Cited by 177Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.

Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

Xi, Zheng-Xiong, Stein, Elliot A.·1999·The Journal of Pharmacology and Experimental Therapeutics

DOI 10.1016/s0022-3565(24)35044-x

Open this paper in CoChat — free account

Abstract

An emerging hypothesis to explain the mechanism of heroin-induced positive reinforcement states that opiates inhibit gamma-aminobutyric acid (GABA)-ergic interneurons within the mesocorticolimbic dopamine (DA) system to disinhibit DA neurons. In support of this hypothesis, we report that the development of heroin self-administration (SA) behavior in drug-naive rats and the maintenance of SA behavior in heroin-trained rats were both suppressed when the GABA(B) receptor agonist baclofen was coadministered with heroin. Microinjections of baclofen into the ventral tegmental area (VTA), but not the nucleus accumbens, decreased heroin reinforcement as indicated by a compensatory increase in SA behavior. Additionally, baclofen administered alone or along with heroin dose-dependently reduced heroin-induced DA release. This effect was blocked partially by intra-VTA infusion of the GABA(B) antagonist 2-hydroxysaclofen, suggesting an additional, perhaps GABA(A) receptor-mediated, disinhibitory effect. Taken together, these experiments, for the first time, demonstrate that heroin-reinforced SA behavior and nucleus accumbens DA release are mediated predominantly by GABA(B) receptors in the VTA and suggest that baclofen may be an effective agent in the treatment of opiate abuse.

Integrity signals

Registry

Crossref · 10.1016/s0022-3565(24)35044-x

Cites

40 of 40 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cellular and molecular mechanisms of drug dependence
Koob, G. F., & Bloom, F. E. (1988) · Science · doi:10.1126/science.2903550 · Cited by 2,070
Opioids excite dopamine neurons by hyperpolarization of local interneurons
Johnson, S., & North, R. (1992) · The Journal of Neuroscience · doi:10.1523/jneurosci.12-02-00483.1992 · Cited by 1,637
Autoradiographic differentiation of mu, delta and kappa opioid receptors in the rat forebrain and midbrain
Mansour, A., Khachaturian, H., Lewis, M. E. S., Akil, H., & Watson, S. J. (1988) · Pain · doi:10.1016/0304-3959(88)90103-0 · Cited by 973
Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats.
Di Chiara, G., & Imperato, A. (1988) · The Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)24578-5 · Cited by 916
GABAA and GABAB receptor site distribution in the rat central nervous system
Bowery, N. G., Hudson, A. L., & Price, G. (1987) · Neuroscience · doi:10.1016/0306-4522(87)90098-4 · Cited by 867
Prefrontal cortical efferents in the rat synapse on unlabeled neuronal targets of catecholamine terminals in the nucleus accumbens septi and on dopamine neurons in the ventral tegmental area
Sesack, S. R., & Pickel, V. M. (1992) · Journal of Comparative Neurology · doi:10.1002/cne.903200202 · Cited by 820
Two types of neurone in the rat ventral tegmental area and their synaptic inputs.
Johnson, S. W., & NORTH, R. A. (1992) · The Journal of Physiology · doi:10.1113/jphysiol.1992.sp019136 · Cited by 672
Destruction of dopamine in the nucleus accumbens selectively attenuates cocaine but not heroin self-administration in rats
Pettit, H. O., Ettenberg, A., Bloom, F. E., & Koob, G. F. (1984) · Psychopharmacology · doi:10.1007/bf00427441 · Cited by 651
Heroin and cocaine intravenous self-administration in rats: Mediation by separate neural systems
Ettenberg, A., Pettit, H. O., Bloom, F. E., & Koob, G. F. (1982) · Psychopharmacology · doi:10.1007/bf00428151 · Cited by 563
The Effects of Opioid Peptides on Dopamine Release in the Nucleus Accumbens: An In Vivo Microdialysis Study
Spanagel, R., Herz, A., & Shippenberg, T. S. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb04963.x · Cited by 539

Show all 40 references

Research works printed but not linked: 1

Ling, 1998, Baclofen as a cocaine anti-craving medication: A preliminary clinical study., Neuropsychopharmacology, 18, 403

Sorted by citations

Molecular Structure and Physiological Functions of GABA B Receptors
Bettler, B., Kaupmann, K., Mosbacher, J., & Gassmann, M. (2004) · Physiological Reviews · doi:10.1152/physrev.00036.2003 · Cited by 943
“Altogether, it appears that GABAB activity blocks the increase in dopamine release that is otherwise induced by drugs of abuse (351).”
Background
The mesolimbic dopamine system: The final common pathway for the reinforcing effect of drugs of abuse?
Pierce, R. C., & Kumaresan, V. (2006) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2005.04.016 · Cited by 913
International Union of Pharmacology. XXXIII. Mammalian γ-Aminobutyric AcidB Receptors: Structure and Function
Bowery, N. G., Bettler, B., Froestl, W., Gallagher, J. P., Marshall, F. H., Raiteri, M., Bonner, T. I., & Enna, S. J. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.2.247 · Cited by 610
“The importance of these observations in the possible treatment of drug abuse is reinforced by the finding that baclofen reduces craving for a host of addictive substances, including heroin, alcohol, and nicotine (Xi and Stein, 1999; Corrigall et al., 2000; Lobina et al., 2000).”
Background
Glutamatergic mechanisms in schizophrenia
Tsai, G., & Coyle, J. T. (2002) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.42.082701.160735 · Cited by 577
Multi-target strategies for the improved treatment of depressive states: Conceptual foundations and neuronal substrates, drug discovery and therapeutic application
Millan, M. J. (2006) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.11.006 · Cited by 569
GABA, ?-hydroxybutyric acid, and neurological disease
Wong, C. G. T., Bottiglieri, T., & Snead, O. C. (2003) · Annals of Neurology · doi:10.1002/ana.10696 · Cited by 489
Neurobiology of addiction
Goodman, A. (2007) · Biochemical Pharmacology · doi:10.1016/j.bcp.2007.07.030 · Cited by 445
Endocannabinoid signaling system and brain reward: emphasis on dopamine
GARDNER, E. (2005) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2005.01.032 · Cited by 387
Pain relief produces negative reinforcement through activation of mesolimbic reward-valuation circuitry
Navratilova, E., Xie, J. Y., Okun, A., Qu, C., Eyde, N., Ci, S., Ossipov, M. H., King, T., Fields, H. L., & Porreca, F. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1214605109 · Cited by 313
Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings
Dichter, G. S., Damiano, C. A., & Allen, J. A. (2012) · Journal of Neurodevelopmental Disorders · doi:10.1186/1866-1955-4-19 · Cited by 299
“Afferents from the VTA of the mesolimbic DA system project outward, and primarily terminate onto the MSNs, which are the principal cell type in the NAc, and produce and secrete GABA, the main inhibitory neurotransmitter used in the CNS.”
BackgroundInfluential
GABAB Receptors: A New Paradigm in G Protein Signaling
Couve, A., Moss, S. J., & Pangalos, M. N. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0908 · Cited by 278
Neural Systems Underlying Opiate Addiction
De Vries, T. J., & Shippenberg, T. S. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-09-03321.2002 · Cited by 270
“Heroin self-administration in rats is associated with both tonic and phasic increases in NAc DA release and is attenuated by the intra-VTA infusion of a GABA-B receptor antagonist (Kiyatkin et al., 1993; Xi and Stein, 1999).”
Background
GABAB receptor agonists for the treatment of drug addiction: a review of recent findings
Cousins, M. S., Roberts, D. C. S., & de Wit, H. (2002) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(01)00163-6 · Cited by 240
“One study has reported that baclofen reduces self-administration of heroin (Xi and Stein, 1999).”
BackgroundInfluential
COMPLETE AND PROLONGED SUPPRESSION OF SYMPTOMS AND CONSEQUENCES OF ALCOHOL-DEPENDENCE USING HIGH-DOSE BACLOFEN: A SELF-CASE REPORT OF A PHYSICIAN
Ameisen, O. (2004) · Alcohol and Alcoholism · doi:10.1093/alcalc/agh130 · Cited by 229
“(ii) In rats, at doses up to 10 times higher (5 mg/kg), baclofen suppresses cocaine self-administration, motivation to consume alcohol and attenuates self-administration of cocaine, alcohol, heroin, nicotine and D-amphetamine (Roberts and Andrews, 1997; Shoaib et al., 1998; Xi and Stein, 1999; Colombo et al., 2000, 20…”
BackgroundInfluential
Critical assessment of how to study addiction and its treatment: Human and non-human animal models
O’Brien, C. P., & Gardner, E. L. (2005) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2005.06.018 · Cited by 224
Ability of Baclofen in Reducing Alcohol Intake and Withdrawal Severity: I???Preclinical Evidence
Colombo, G., Agabio, R., Carai, M. A. M., Lobina, C., Pani, M., Reali, R., Addolorato, G., & GESSA, G. L. (2000) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2000.tb04554.x · Cited by 208
Allosteric Modulation of Family C G-Protein-Coupled Receptors: from Molecular Insights to Therapeutic Perspectives
Urwyler, S. (2011) · Pharmacological Reviews · doi:10.1124/pr.109.002501 · Cited by 210
Baclofen antagonizes nicotine‐, cocaine‐, and morphine‐induced dopamine release in the nucleus accumbens of rat
Fadda, P., Scherma, M., Fresu, A., Collu, M., & Fratta, W. (2003) · Synapse · doi:10.1002/syn.10238 · Cited by 200
“…(Roberts et al., 1996; Roberts and Andrews, 1997; Shoaib et al., 1998; Brebner et al., 2000) methamphetamine (Ranaldi and Poeggel, 2002), heroin (Xi and Stein, 1999, 2000, 2002; Brebner et al., 2002), nicotine (Corrigall et al., 2000, 2001; Fattore et al., 2002), gammahydroxybutiric acid…”
Background
Theγ‐Aminobutyric Acid‐B Receptor Agonist Baclofen Attenuates Responding for Ethanol in Ethanol‐Dependent Rats
Walker, B. M., & Koob, G. F. (2006) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2006.00259.x · Cited by 196
“…tegmental area (VTA), nucleus accumbens (NAc), and the central nucleus of the amygdala (CeA; Bowery et al., 1987; Cousins et al., 2002; Fadda et al., 2003; Xi and Stein, 1999), which are likely candidates as the site(s) of action for baclofen to modulate ethanol self-administration behavior.”
Background
Dopamine signaling in the nucleus accumbens of animals self-administering drugs of abuse
Willuhn, I., Wanat, M. J., Clark, J. J., & Phillips, P. E. M. (2010) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2009_27 · Cited by 193
“In contrast, lesion or inactivation of the mesolimbic dopamine system in the VTA (Roberts and Koob 1982; Shoaib et al. 1998; Xi and Stein 1999) or the NAcc (Roberts et al. 1977, 1980; Lyness et al. 1979; Pettit et al. 1984; Corrigall et al. 1992; Shoaib et al. 1998) attenuate cocaine, amphetamine, heroin, and nicotine…”
Influential
The somatodendritic release of dopamine in the ventral tegmental area and its regulation by afferent transmitter systems
Adell, A., & Artigas, F. (2004) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2004.05.001 · Cited by 197
A POTENTIAL ROLE FOR GABAB AGONISTS IN THE TREATMENT OF PSYCHOSTIMULANT ADDICTION
Brebner, K. (2002) · Alcohol and Alcoholism · doi:10.1093/alcalc/37.5.478 · Cited by 166
“Several other reports indicate that intra-VTA baclofen also inhibits heroin (Xi and Stein, 1999) and nicotine (Corrigall et al., 2000) self-administration, intracranial selfstimulation (Willick and Kokkinidis, 1995; Panagis and Kastellakis, 2002) and morphine place preference (Tsuji et al., 1996).”
Background
Development of pharmacotherapies for drug addiction: a Rosetta stone approach
Koob, G. F., Kenneth Lloyd, G., & Mason, B. J. (2009) · Nature Reviews Drug Discovery · doi:10.1038/nrd2828 · Cited by 154
Baclofen for Alcohol Dependence: A Preliminary Open‐Label Study
Flannery, B., Garbutt, J. C., Cody, M. W., Renn, W., Grace, K., Osborne, M., Crosby, K., Morreale, M. K., & Trivette, A. (2004) · Alcoholism Clinical and Experimental Research · doi:10.1097/01.alc.0000141640.48924.14 · Cited by 152
Sugar addiction: the state of the science
Westwater, M. L., Fletcher, P. C., & Ziauddeen, H. (2016) · Zeitschrift für Ernährungswissenschaft · doi:10.1007/s00394-016-1229-6 · Cited by 148
“As heroin has high affinity for MOR and delta opioid receptors (DOR), administration of selective MOR and DA agonists has been shown to result in heroin reinforcement that is extinguished following chemical lesioning of DA neurons or microinjections of opioid receptor antagonists within the VTA [65].”
Background
What We Have Learned about Addiction from Animal Models of Drug Self‐Administration
Gardner, E. L. (2000) · American Journal on Addictions · doi:10.1080/105504900750047355 · Cited by 130
NIDA’s medication development priorities in response to the Opioid Crisis: ten most wanted
Rasmussen, K., White, D. A., & Acri, J. B. (2019) · Neuropsychopharmacology · doi:10.1038/s41386-018-0292-5 · Cited by 128
Role of GABAB receptor in alcohol dependence: Reducing effect of baclofen on alcohol intake and alcohol motivational properties in rats and amelioration of alcohol withdrawal syndrome and alcohol craving in human alcoholics
Colombo, G., Addolorato, G., Agabio, R., Carai, M. A. M., Pibiri, F., Serra, S., Vacca, G., & Gessa, G. L. (2004) · Neurotoxicity Research · doi:10.1007/bf03033315 · Cited by 130
Chemistry and Pharmacology of GABAB Receptor Ligands
Froestl, W. (2010) · Advances in pharmacology · doi:10.1016/s1054-3589(10)58002-5 · Cited by 125
“Riahi et al., 2009; Sahraei et al., 2009; Zarrindast et al., 2008) and for the prevention of heroin-seeking behavior (Spano et al., 2007; Xi & Stein, 1999).”
GABAergic MECHANISMS OF OPIATE REINFORCEMENT
Xi, Z. (2002) · Alcohol and Alcoholism · doi:10.1093/alcalc/37.5.485 · Cited by 127
Self-citation
Cannabinoid Modulation of Opiate Reinforcement through the Ventral Striatopallidal Pathway
Caillé, S., & Parsons, L. H. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300848 · Cited by 122
“Intra-ventral tegmental area opiate administration has been shown to inhibit GABAergic interneuronal input to dopamine (DA) cells, thereby increasing the firing of midbrain DA cells that terminate in the NAC (Johnson and North, 1992; Wise et al, 1995; Xi and Stein, 2000) and increasing NAC DA release (Hemby et al, 199…”
Background
Effectiveness and Safety of Baclofen in the Treatment of Alcohol Dependent Patients
Leggio, L., Garbutt, J. C., & Addolorato, G. (2010) · CNS & Neurological Disorders - Drug Targets · doi:10.2174/187152710790966614 · Cited by 116
Dopamine in the Brain: Hypothesizing Surfeit or Deficit Links to Reward and Addiction
Blum, K., Thanos, P. K., & Oscar‐Berman, M. (2015) · Journal of Reward Deficiency Syndrome · doi:10.17756/jrds.2015-016 · Cited by 121
The GABAB Receptor-Positive Modulator GS39783 and the GABAB Receptor Agonist Baclofen Attenuate the Reward-Facilitating Effects of Cocaine: Intracranial Self-Stimulation Studies in the Rat
Slattery, D. A., Markou, A., Froestl, W., & Cryan, J. F. (2005) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300734 · Cited by 111
“et al, 2002; Paterson et al, 2004a, b), heroin (Xi and Stein, 1999; Di Ciano and Everitt, 2003) alcohol (Colombo et al, 2002), and cocaine (Roberts et al, 1996; Brebner et al, 2000, 2002b).”
BackgroundInfluential
GABAB Receptors in Reward Processes
Vlachou, S., & Markou, A. (2010) · Advances in pharmacology · doi:10.1016/s1054-3589(10)58013-x · Cited by 110
Repeated Administration of the GABAB Receptor Agonist CGP44532 Decreased Nicotine Self-Administration, and Acute Administration Decreased Cue-Induced Reinstatement of Nicotine-Seeking in Rats
Paterson, N. E., Froestl, W., & Markou, A. (2004) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300524 · Cited by 108
The GABA B agonist baclofen reduces cigarette consumption in a preliminary double-blind placebo-controlled smoking reduction study
Franklin, T. R., Harper, D., Kampman, K. M., Kildea-McCrea, S., Jens, W., Lynch, K. G., O’Brien, C. P., & Childress, A. R. (2009) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2009.02.014 · Cited by 105
GABAB Receptors and Depression: Current Status
Cryan, J. F., & Slattery, D. A. (2010) · Advances in pharmacology · doi:10.1016/s1054-3589(10)58016-5 · Cited by 106
BACLOFEN ANTAGONIZES INTRAVENOUS SELF-ADMINISTRATION OF NICOTINE IN MICE AND RATS
Fattore, L. (2002) · Alcohol and Alcoholism · doi:10.1093/alcalc/37.5.495 · Cited by 100
The GABAB Receptor Agonist Baclofen Attenuates Cocaine- and Heroin-Seeking Behavior by Rats
Ciano, P. D., & Everitt, B. J. (2002) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300088 · Cited by 99
“In this regard, the dose of heroin used in the present study (0.12 mg/kg/ infusion) was high relative to the dose used in other studies (0.06 mg/kg/infusion (Xi and Stein, 1999, 2000); 0.025 mg/kg/ infusion (Brebner et al, 2002)).”
BackgroundResultInfluential
Increased Mesolimbic GABA Concentration Blocks Heroin Self-Administration in the Rat
Xi, Z., & Stein, E. A. (2000) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(24)39113-x · Cited by 95
Self-citation
Intra-VTA Baclofen Attenuates Cocaine Self-Administration on a Progressive Ratio Schedule of Reinforcement
Brebner, K. (2000) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(00)00286-0 · Cited by 90
Effect of Baclofen on Alcohol and Sucrose Self-Administration in Rats
Anstrom, K. K., Cromwell, H. C., Markowski, T., & Woodward, D. J. (2003) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2003.tb04414.x · Cited by 86
Acquisition of drug self-administration: Environmental and pharmacological interventions.
Campbell, U. C., & Carroll, M. E. (2000) · Experimental and Clinical Psychopharmacology · doi:10.1037/1064-1297.8.3.312 · Cited by 85
Baclofen Blocks Expression and Sensitization of Anxiety‐Like Behavior in an Animal Model of Repeated Stress and Ethanol Withdrawal
Knapp, D. J., Overstreet, D. H., & Breese, G. R. (2007) · Alcoholism Clinical and Experimental Research · doi:10.1111/j.1530-0277.2007.00342.x · Cited by 85
“The suppression of alcohol self-administration by baclofen is consistent with other preclinical literature in which the drug reduced self-administration of cocaine (Campbell et al., 1999), amphetamines (Phillis et al., 2001), heroin (Xi and Stein, 1999), and nicotine (Corrigall et al., 2001).”
Result
Serotonin–GABA interactions modulate MDMA‐induced mesolimbic dopamine release
Bankson, M. G., & Yamamoto, B. K. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02763.x · Cited by 82
Baclofen decreases methamphetamine self-administration in rats
Ranaldi, R., & Poeggel, K. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00007 · Cited by 82
Allelic association analysis of the dopamine D2, D3, 5‐HT2A, and GABAAγ2 receptors and serotonin transporter genes with heroin abuse in Chinese subjects
Li, T., Liu, X., Zhao, J., Hu, X., Ball, D. M., Loh, E., Sham, P. C., & Collier, D. A. (2002) · American Journal of Medical Genetics · doi:10.1002/ajmg.10200 · Cited by 81
A Possible Mechanism Underlying the Effectiveness of Acupuncture in the Treatment of Drug Addiction
Yang, C. H., Lee, B. H., & Sohn, S. H. (2007) · Evidence-based Complementary and Alternative Medicine · doi:10.1093/ecam/nem081 · Cited by 81
“A similar conclusion was obtained in another study in which GABAB receptor agonist baclofen dose dependently reduced heroin-induced dopamine release in the nucleus accumbens and inhibited heroin self-administration behavior (37).”
Result
Effects of acute acamprosate and homotaurine on ethanol intake and ethanol-stimulated mesolimbic dopamine release
Olive, M. F., Nannini, M., Ou, C. J., Koenig, H. N., & Hodge, C. W. (2002) · European Journal of Pharmacology · doi:10.1016/s0014-2999(02)01272-4 · Cited by 81
Acupuncture-mediated inhibition of ethanol-induced dopamine release in the rat nucleus accumbens through the GABAB receptor
Yoon, S. S., Kwon, Y. K., Kim, M.-R., Shim, I., Kim, K. J., Lee, M. H., Lee, Y., Golden, G. T., & Yang, C. H. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.07.095 · Cited by 79
Baclofen for maintenance treatment of opioid dependence: A randomized double-blind placebo-controlled clinical trial [ISRCTN32121581]
Assadi, S. M., Radgoodarzi, R., & Abhari, S. A. A. (2003) · BMC Psychiatry · doi:10.1186/1471-244x-3-16 · Cited by 79
“However, while preclinical studies support the idea that baclofen may help maintaining abstinence from opioids via reducing both the positive reinforcing (reward) properties [10,22] and negative reinforcement (withdrawal) of opioids [11,12]; to the best of our knowledge, there is no reported clinical trial that has ev…”
Influential
Endogenous opiates: 1999
Vaccarino, A. L., & Kastin, A. J. (2000) · Peptides · doi:10.1016/s0196-9781(00)00345-4 · Cited by 79
SR141716A reduces the reinforcing properties of heroin but not heroin‐induced increases in nucleus accumbens dopamine in rats
Caillé, S., & Parsons, L. H. (2003) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2003.02961.x · Cited by 83
Attenuation of d-amphetamine self-administration by baclofen in the rat: behavioral and neurochemical correlates
Brebner, K., Ahn, S., & Phillips, A. G. (2004) · Psychopharmacology · doi:10.1007/s00213-004-1968-6 · Cited by 77
“Local infusion of baclofen into the VTA reduces IVSA of cocaine (Brebner et al. 2000b) and heroin (Xi and Stein 1999) and also decreases DA efflux in the NAc (Yoshida et al. 1994; Westerink et al. 1996, 1997).”
Sex differences in the effects of baclofen on the acquisition of intravenous cocaine self-administration in rats
Campbell, U. C., Morgan, A. D., & Carroll, M. E. (2002) · Drug and Alcohol Dependence · doi:10.1016/s0376-8716(01)00185-5 · Cited by 77
“Furthermore, previous studies have shown that at the dose used in the present study, baclofen had no effect on operant food-maintained responding in rats (Roberts et al., 1996; Roberts and Andrews, 1997; Shoaib et al., 1998; Xi and Stein, 1999).”
BackgroundResult
GABAB receptor alterations as indicators of physiological and pharmacological function
Enna, S. J., & Bowery, N. G. (2004) · Biochemical Pharmacology · doi:10.1016/j.bcp.2004.06.037 · Cited by 77
Preclinical evidence for GABAB agonists as a pharmacotherapy for cocaine addiction
Roberts, D. C. S. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.06.017 · Cited by 76
PKG and PKA Signaling in LTP at GABAergic Synapses
Nugent, F. S., Niehaus, J. L., & Kauer, J. A. (2009) · Neuropsychopharmacology · doi:10.1038/npp.2009.5 · Cited by 73
“…properties of intracranial self-stimulation (Willick and Kokkinidis, 1995), with self-administration of several addictive drugs including heroin (Xi and Stein, 1999), with morphine-induced place preference (Tsuji et al, 1996), and with opioid-induced motor sensitization (Leite-Morris et al,…”
Fentanyl vapor self-administration model in mice to study opioid addiction
Moussawi, K., Ortiz, M. M., Gantz, S. C., Tunstall, B. J., Marchette, R. C. N., Bonci, A., Koob, G. F., & Vendruscolo, L. F. (2020) · Science Advances · doi:10.1126/sciadv.abc0413 · Cited by 70
“Furthermore, GABAB receptor agonism by direct agonists or positive allosteric modulators in the VTA blocks dopamine release in response to drugs (22, 23), reduces the reinforcing properties of drugs, and inhibits the reinstatement of drug seeking in models of opioids and other drugs of abuse (47).”
Background
In vivo modulation of ventral tegmental area dopamine and glutamate efflux by local GABAB receptors is altered after repeated amphetamine treatment
Giorgetti, M., Hotsenpiller, G., Froestl, W., & Wolf, M. E. (2002) · Neuroscience · doi:10.1016/s0306-4522(01)00510-3 · Cited by 72
Baclofen reduces fat intake under binge-type conditions
Buda-Levin, A., Wojnicki, F. H. E., & Corwin, R. L. (2005) · Physiology & Behavior · doi:10.1016/j.physbeh.2005.07.020 · Cited by 71
Hypothesis-Driven Medication Discovery for the Treatment of Psychostimulant Addiction
Xi, Z., & Gardner, E. L. (2008) · Current Drug Abuse Reviews · doi:10.2174/1874473710801030303 · Cited by 70
“This is consistent with previous findings that local NAc perfusion of GABAA or GABAB receptor agonists, but not GABA itself, inhibits NAc DA and glutamate [127, 153, 154], and similarly inhibits cocaine or heroin self-administration and reinstatement of drug-seeking behaviors [154, 155].”
ResultSelf-citation
GABAB Receptor Activation in the Ventral Tegmental Area Inhibits the Acquisition and Expression of Opiate-Induced Motor Sensitization
Leite‐Morris, K. A., Fukudome, E. Y., Shoeb, M. H., & Kaplan, G. B. (2004) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.103.058412 · Cited by 70
The GABAB receptor agonist baclofen prevents heroin-induced reinstatement of heroin-seeking behavior in rats
Spano, M. S., Fattore, L., Fratta, W., & Fadda, P. (2007) · Neuropharmacology · doi:10.1016/j.neuropharm.2007.02.012 · Cited by 68
Baclofen prevents drug-induced reinstatement of extinguished nicotine-seeking behaviour and nicotine place preference in rodents
Fattore, L., Spano, M. S., Cossu, G., Scherma, M., Fratta, W., & Fadda, P. (2009) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2009.01.007 · Cited by 68
“, 1998), heroin (Xi and Stein, 1999), alcohol (Anstrom et al.”
Baclofen suppresses binge eating of pure fat but not a sugar-rich or sweet–fat diet
Berner, L. A., Bocarsly, M. E., Hoebel, B. G., & Avena, N. M. (2009) · Behavioural Pharmacology · doi:10.1097/fbp.0b013e328331ba47 · Cited by 65
“When injected into the ventral tegmental area, baclofen also reduces the reinforcing effects of heroin (Xi and Stein, 1999), although this effect is not observed when baclofen is given i.p. (Di Ciano and Everitt, 2003).”
Background
Further evidence that the delayed temporal dopaminergic effects of LSD are mediated by a mechanism different than the first temporal phase of action
Marona‐Lewicka, D., & Nichols, D. E. (2007) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2007.06.001 · Cited by 64
“GABA-B receptors are localized on dopaminergic neurons and their stimulation by baclofen can attenuate dopaminergic activity (Westerink et al., 1996; Xi and Stein, 1999).”
Background
Acupuncture suppresses morphine self-administration through the GABA receptors
Yoon, S. S., Kim, H., Choi, K., Lee, B. H., Lee, Y. K., Lim, S. C., Choi, S. H., Hwang, M., Kim, K. J., & Yang, C. H. (2010) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2009.12.011 · Cited by 63
Effects of GABAB receptor agents on cocaine priming, discrete contextual cue and food induced relapses
Filip, M., & Frankowska, M. (2007) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2007.05.069 · Cited by 63
Cannabinoid Transmission in the Prefrontal Cortex Bi-Phasically Controls Emotional Memory Formation via Functional Interactions with the Ventral Tegmental Area
Draycott, B., Loureiro, M., Ahmad, T., Tan, H., Zunder, J. S., & Laviolette, S. R. (2014) · Journal of Neuroscience · doi:10.1523/jneurosci.1297-14.2014 · Cited by 63
“…not exclusively) localized to nonDAergic GABAergic VTA neurons (Churchill et al., 1992; Kalivas, 1993), GABAB receptors are more localized on VTA DA neurons (Margeta-Mitrovic et al., 1992; Xi and Stein, 1999) and directly inhibit the activity VTA DA neuron activity (Margolis et al., 2012).”
Background
The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction
Guo, Y., Wang, H., Xiang, X., & Zhao, Y. (2009) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2009.02.005 · Cited by 62
“Microinjection of baclofen into the VTA activated GABAB receptors and blocked self-administration behaviors induced by heroin, DA release in the NAc (Xi and Stein, 1998, 1999) and morphine-induced CPP (Tsuji et al., 1996).”
Background
Clinical Potential of GABABReceptor Modulators
Ong, J. A., & Kerr, D. I. B. (2005) · CNS Drug Reviews · doi:10.1111/j.1527-3458.2005.tb00049.x · Cited by 59
“Baclofen has been shown to antagonize the rewarding effects induced by nicotine in rodents (33), and to inhibit heroin self-administration (100).”
Background
Role of γ‐Aminobutyric Acid (GABA) and Metabotropic Glutamate Receptors in Nicotine Reinforcement: Potential Pharmacotherapies for Smoking Cessation
Markou, A., Paterson, N. E., & Semenova, S. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1316.061 · Cited by 56
Efficacy and Tolerability of Baclofen in Substance Use Disorders: A Systematic Review
Agabio, R., Preti, A., & Gessa, G. L. (2013) · European Addiction Research · doi:10.1159/000347055 · Cited by 56
Increased gabaergic input to ventral tegmental area dopaminergic neurons associated with decreased cocaine reinforcement in μ-opioid receptor knockout mice
Mathon, D. S., Lesscher, H. M. B., Gerrits, M. A. F. M., Kamal, A., Pintar, J. E., Schuller, A. G., Spruijt, B. M., Burbach, J. P. H., Smidt, M. P., van Ree, J. M., et al. (2004) · Neuroscience · doi:10.1016/j.neuroscience.2004.10.002 · Cited by 55
GABA Modulation of Cocaine Self‐Administration
Roberts, D. C. S., & Brebner, K. (2000) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2000.tb06680.x · Cited by 54
The effect of baclofen alone and in combination with naltrexone on ethanol consumption in the rat
Stromberg, M. F. (2004) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2004.05.006 · Cited by 54
Historical Perspective and Emergence of the GABAB Receptor
Bowery, N. G. (2010) · Advances in pharmacology · doi:10.1016/s1054-3589(10)58001-3 · Cited by 51
GABAB receptors and synaptic modulation
Kornau, H. (2006) · Cell and Tissue Research · doi:10.1007/s00441-006-0264-7 · Cited by 53
“in both animals and man (Xi and Stein 1999; Cousins et al. 2002; Slattery et al. 2005).”
Background
PRECLINICAL STUDY: Baclofen reduces ethanol intake in high‐alcohol‐drinking University of Chile bibulous rats
Quintanilla, M. E., Perez, E., & Tampier, L. (2008) · Addiction Biology · doi:10.1111/j.1369-1600.2008.00102.x · Cited by 49
“The GABAB receptor is located within reinforcement systems (Xi & Stein 1999; Cousins, Roberts & de Wit 2002; Fadda et al. 2003) and through both presynaptic and postsynaptic mechanisms has been hypothesized to modulate a variety of drug- and alcohol-related reward and reinforcement behavior…”
Background
Intravenous heroin self‐administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in rats
Caillé, S., & Parsons, L. H. (2004) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2004.03497.x · Cited by 48
Inhibition of kynurenine aminotransferase II reduces activity of midbrain dopamine neurons
Linderholm, K. R., Tufvesson‐Alm, M., Larsson, M. K., Olsson, S. K., Goiny, M., Hajós, M., Erhardt, S., & Engberg, G. (2015) · Neuropharmacology · doi:10.1016/j.neuropharm.2015.10.028 · Cited by 44
Reduction of excessive alcohol drinking by a novel GABAB receptor positive allosteric modulator ADX71441 in mice
Hwa, L. S., Kalinichev, M., Haddouk, H., Poli, S. M., & Miczek, K. A. (2013) · Psychopharmacology · doi:10.1007/s00213-013-3245-z · Cited by 44
“Activation of the GABAB receptor reduces the reinforcing properties of cocaine, heroin, and nicotine (Cousins et al. 2002; Fadda et al. 2003; Xi and Stein 1999; Vlachou et al. 2011).”
Isoliquiritigenin suppresses cocaine-induced extracellular dopamine release in rat brain through GABAB receptor
Jang, E. Y., Choe, E. S., Hwang, M., Kim, S. C., Lee, J. R., Kim, S. G., Jeon, J., Buono, R. J., & Yang, C. H. (2008) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2008.03.054 · Cited by 43
Inhibition of Baclofen on morphine-induced hyperactivity, reverse tolerance and postsynaptic dopamine receptor supersensitivity
Woo, S.-H., Kim, H.-S., Yun, J.-S., Lee, M.-K., Oh, K., Seong, Y.-H., Oh, S., & Jang, C. (2001) · Pharmacological Research · doi:10.1006/phrs.2000.0789 · Cited by 41
Emerging drugs to treat alcoholism
Soyka, M., & Rösner, S. (2010) · Expert Opinion on Emerging Drugs · doi:10.1517/14728214.2010.500811 · Cited by 42
“The GABAB receptor consists of two subunits (GABR1 and GABR2) and is located with high density within the brain reward system [108-111], where it modulates a number of alcoholrelated reward and reinforcement mechanisms [108,112].”
Background
Acupuncture reduces relapse to cocaine‐seeking behavior via activation of GABA neurons in the ventral tegmental area
Jin, W., Kim, M. S., Jang, E. Y., Lee, J. Y., Lee, J. G., Kim, H. Y., Yoon, S. S., Lee, B. H., Chang, S., Kim, J. H., et al. (2017) · Addiction Biology · doi:10.1111/adb.12499 · Cited by 39
“GABAB receptors are expressed more on DA neurons than GABA interneurons in the VTA (Xi & Stein 1999), suppress DA neurons directly (Xi & Stein 1999; Margolis et al. 2012) and inhibit the reinforcing effects of cocaine (Brebner et al. 2000).”
Cocaine and heroin (‘speedball’) self-administration: the involvement of nucleus accumbens dopamine and μ-opiate, but not δ-opiate receptors
Cornish, J. L., Lontos, J. M., Clemens, K. J., & McGregor, I. S. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2135-9 · Cited by 41
“Conversely, the reinforcing efficacy of heroin is reduced following inhibition of dopaminergic cells in the VTA which is accompanied by a significant reduction in nucleus accumbens extracellular dopamine levels (Xi and Stein 1999).”
Background
Effects of baclofen on conditioned rewarding and discriminative stimulus effects of nicotine in rats
Foll, B. L., Wertheim, C. E., & Goldberg, S. R. (2008) · Neuroscience Letters · doi:10.1016/j.neulet.2008.07.074 · Cited by 41
Baclofen inhibits opiate-induced conditioned place preference and associated induction of Fos in cortical and limbic regions
Kaplan, G. B., Leite‐Morris, K. A., Joshi, M., Shoeb, M. H., & Carey, R. J. (2003) · Brain Research · doi:10.1016/s0006-8993(03)03218-9 · Cited by 39
Failure of baclofen to modulate discriminative–stimulus effects of cocaine or methamphetamine in rats
Munzar, P., Kutkat, S. W., Miller, C. R., & Goldberg, S. R. (2000) · European Journal of Pharmacology · doi:10.1016/s0014-2999(00)00772-x · Cited by 39
Effects of high-dose baclofen on cue reactivity in alcohol dependence: A randomized, placebo-controlled pharmaco-fMRI study
Beck, A., Pelz, P., Lorenz, R. C., Charlet, K., Geisel, O., Heinz, A., Wüstenberg, T., & Müller, C. A. (2018) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2018.08.507 · Cited by 38
Pharmacotherapy of alcoholic liver disease in clinical practice
Rosato, V., Abenavoli, L., Federico, A., Masarone, M., & Persico, M. (2015) · International Journal of Clinical Practice · doi:10.1111/ijcp.12764 · Cited by 37
GABAergic mechanisms of heroin‐induced brain activation assessed with functional MRI
Xi, Z., Wu, G., Stein, E. A., & Li, S. (2002) · Magnetic Resonance in Medicine · doi:10.1002/mrm.10282 · Cited by 36
Self-citation
The gamma-aminobutyric acid type B (GABAB) receptor agonist baclofen inhibits morphine sensitization by decreasing the dopamine level in rat nucleus accumbens
Fu, Z., Yang, H., Xiao, Y., Zhao, G., & Huang, H. (2012) · Behavioral and Brain Functions · doi:10.1186/1744-9081-8-20 · Cited by 33
“Discussion In recent years, GABAB receptor agonist has received a considerable research interest for its extensive therapeutic implications associated with alcohol dependence [28], cocaine abuse [20,29], nicotine [30,31] and opiates addiction [32-34].”
Systemic administration of 1R,4S-4-amino-cyclopent-2-ene-carboxylic acid, a reversible inhibitor of GABA transaminase, blocks expression of conditioned place preference to cocaine and nicotine in rats
Ashby, C. R., Paul, M., Gardner, E. L., Gerasimov, M. R., Dewey, S. L., Lennon, I. C., & Taylor, S. J. (2002) · Synapse · doi:10.1002/syn.10052 · Cited by 32
“Furthermore, a number of studies have shown that the GABAB receptor agonist baclofen attenuates cocaine (Brebner et al., 2000; Roberts et al., 1996) and heroin (Xi and Stein, 1999) selfadministration in rats.”
Background
Baclofen antagonises intravenous self-administration of γ-hydroxybutyric acid in mice
Fattore, L., Cossu, G., Martellotta, M. C., Deiana, S., & Fratta, W. (2001) · Neuroreport · doi:10.1097/00001756-200107200-00039 · Cited by 32
Effects of dextromethorphan on dopamine release in the nucleus accumbens: Interactions with morphine
Steinmiller, C. L. (2003) · Pharmacology Biochemistry and Behavior · doi:10.1016/s0091-3057(02)01080-8 · Cited by 33
GABAB receptors within the ventral tegmental area are involved in the expression and acquisition of morphine-induced place preference in morphine-sensitized rats
Sahraei, H., Etemadi, L., Rostami, P., Pourmotabbed, A., Zarrindast, M., Shams, J., Ghoshooni, H., Noroozzadeh, A., Esfandiari, B., & Salimi, S. H. (2008) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2008.08.015 · Cited by 31

Authors: Xi, Z.-X., & Stein, E. A.
Affiliations: Medical College of Wisconsin (US)
ORCID: Xi, Zheng-Xiong
Stein, Elliot A.
Venue: The Journal of Pharmacology and Experimental Therapeutics
Publisher: Elsevier BV
Published: 1999-09
Volume: 290
Issue: 3
Pages: 1369-1374
ISSN: 0022-3565 (ISSN-L)
DOI: 10.1016/s0022-3565(24)35044-x
OpenAlex: W2164726829
Cited by: 177
References: 40
Citations by year: 2026: 1 · 2025: 2 · 2024: 1 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 3 · 2018: 4 · 2017: 4 · 2016: 6 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 7
FWCI: 4.34
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Journal of Pharmacology and Experimental Therapeutics (publishedVersion)
PubMed (publishedVersion)
PubMed
Funders: National Institute on Drug Abuse (R01DA009465, DA 09465)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Keywords: baclofen, heroin self-administration, GABAB receptors, mesolimbic dopamine system, ventral tegmental area, nucleus accumbens, GABAergic interneurons, disinhibition, 2-hydroxysaclofen, GABAA receptor
MeSH terms: Animals, Baclofen, Behavior, Animal, Heroin, Dopamine, Electrodes, Limbic System, Male, Mesencephalon, Narcotic Antagonists, Narcotics, Nucleus Accumbens, Self Administration, Rats, Sprague-Dawley, Ventral Tegmental Area, GABA Agonists, Substance-Related Disorders, Rats

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks