Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

Xi, Zheng-Xiong; Stein, Elliot A.

doi:10.1016/s0022-3565(24)35044-x

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

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

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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.

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Lesion or inactivation of the mesolimbic DA system in the VTA or NAc decreases cocaine, amphetamine, heroin, and nicotine self-administration in rats.
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From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [138]

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“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
Baclofen decreases methamphetamine self-administration in rats
Ranaldi, R., & Poeggel, K. (2002) · Neuroreport · doi:10.1097/00001756-200207020-00007 · Cited by 82 · see citing works
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 · see citing works
A Possible Mechanism Underlying the Effectiveness of Acupuncture in the Treatment of Drug Addiction
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“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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 80 · see citing works
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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“…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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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 67 · see citing works
“, 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 · see citing works
“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 · see citing works
“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 · see citing works
Effects of GABAB receptor agents on cocaine priming, discrete contextual cue and food induced relapses
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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 · see citing works
“…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 63 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
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 · see citing works
GABAB receptors and synaptic modulation
Kornau, H. (2006) · Cell and Tissue Research · doi:10.1007/s00441-006-0264-7 · Cited by 51 · see citing works
“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 48 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works
“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 · see citing works
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 · see citing works
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“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 · see citing works
“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
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“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 39 · see citing works
Baclofen inhibits opiate-induced conditioned place preference and associated induction of Fos in cortical and limbic regions
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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 · see citing works
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 · see citing works
Pharmacotherapy of alcoholic liver disease in clinical practice
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GABAergic mechanisms of heroin‐induced brain activation assessed with functional MRI
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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 · see citing works
“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 · see citing works
“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 · see citing works
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 · see citing works
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 · see citing works

Baclofen Inhibits Heroin Self-Administration Behavior and
Release, M. D., Xi, Z., & Stein, E. A. (2016)
Self-citation
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 · see citing works
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 · see citing works
Self-citation
The GABA B antagonist CGP56433A attenuates the effect of baclofen on cocaine but not heroin self-administration in the rat
Brebner, K., Froestl, W., & Roberts, D. C. S. (2002) · Psychopharmacology · doi:10.1007/s00213-001-0952-7 · Cited by 31 · see citing works
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 197 · see citing works

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

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Baclofen Inhibits Heroin Self-Administration Behavior and Mesolimbic Dopamine Release

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