Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1

Carlezon, William A.; Haile, Colin N.; Coppersmith, Robert; Hayashi, Yasunori; Malinow, Roberto; Neve, Rachael L.; Nestler, Eric J.

doi:10.1523/jneurosci.20-05-j0002.2000

Cited by 98Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNeuropeptides and Animal Physiology

Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1

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Carlezon, William A., Haile, Colin N., Coppersmith, Robert, Hayashi, Yasunori, Malinow, Roberto, Neve, Rachael L., Nestler, Eric J.·2000·The Journal of Neuroscience

DOI 10.1523/jneurosci.20-05-j0002.2000PMC PMC6772915

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Abstract

Repeated administration of morphine increases expression of GluR1 (an AMPA glutamate receptor subunit) in the ventral tegmental area (VTA) of the midbrain, an important neural substrate for the rewarding actions of morphine. Microinjections of a herpes simplex virus (HSV) vector that causes local overexpression of GluR1 (HSV-GluR1) into the VTA can enhance the ability of morphine to establish conditioned place preferences, suggesting that altered GluR1 expression in this region is directly associated with changes in the rewarding efficacy of morphine. We now report that in rats given HSV-GluR1 directly into the VTA, morphine is most rewarding when maximal transgene expression is in the rostral VTA, whereas morphine is aversive when maximal transgene expression is in the caudal VTA. Dual-labeling immunohistochemistry shows that this difference cannot be explained by a different fraction of dopaminergic neurons infected in the rostral versus caudal VTA. No such anatomical specificity is seen in rats given VTA microinjections of HSV-LacZ, a vector expressing a control protein (-galactosidase). These results suggest that distinct substrates within the VTA itself differentially contribute to the rewarding and aversive properties of opiates.

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Data obtained with viral technology indicate that the anterior and posterior VTA play different roles in conditioned place preference induced by systemic cocaine or opiate administration.
“Data obtained with viral technology also indicate that the anterior and posterior VTA play different roles in conditioned place preference induced by systemic cocaine or opiate administration”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Carlezon et al., 2000

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The rat brain in stereotaxic coordinates
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Sensitization to Morphine Induced by Viral-Mediated Gene Transfer
Carlezon, W. A., Boundy, V. A., Haile, C. N., Lane, S. B., Kalb, R. G., Neve, R. L., & Nestler, E. J. (1997) · Science · doi:10.1126/science.277.5327.812 · Cited by 279 · cited 7× · see citing works
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BackgroundMethodResultInfluential
Reinforcing effects of morphine in the nucleus accumbens
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Introduction of the glutamate receptor subunit 1 into motor neurons in vitro and in vivo using a recombinant herpes simplex virus
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Background
Ventral tegmental area region governs GABAB receptor modulation of ethanol-stimulated activity in mice
Boehm, S. L., Piercy, M., Bergstrom, H. C., & Phillips, T. J. (2002) · Neuroscience · doi:10.1016/s0306-4522(02)00378-0 · Cited by 72 · see citing works
Early Odor Preference Learning in the Rat: Bidirectional Effects of cAMP Response Element-Binding Protein (CREB) and Mutant CREB Support a Causal Role for Phosphorylated CREB
Yuan, Q., Harley, C. W., Darby‐King, A., Neve, R. L., & McLean, J. H. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-11-04760.2003 · Cited by 70 · see citing works
Dissociation between Rewarding and Psychomotor Effects of Opiates: Differential Roles for Glutamate Receptors within Anterior and Posterior Portions of the Ventral Tegmental Area
Shabat-Simon, M., Levy, D. J., Amir, A., Rehavi, M., & Zangen, A. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.1958-08.2008 · Cited by 70 · see citing works
Voluntary wheel running modulates glutamate receptor subunit gene expression and stress hormone release in Lewis rats
Makatsori, A., Dunčko, R., Schwendt, M., Moncek, F., Johansson, B. B., & Ježová, D. (2003) · Psychoneuroendocrinology · doi:10.1016/s0306-4530(02)00062-8 · Cited by 67 · see citing works
Pharmacological recruitment of the GABAergic tail of the ventral tegmental area by acute drug exposure
Kaufling, J., Waltisperger, E., Bourdy, R., Valera, A. M., Veinante, P., Freund‐Mercier, M. J., & Barrot, M. (2010) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2010.00984.x · Cited by 66 · see citing works
Repeated Administration of Amphetamine or Cocaine Does Not Alter AMPA Receptor Subunit Expression in the Rat Midbrain,
Lü, W. (2002) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00272-x · Cited by 63 · see citing works
Phospholipase Cγ in Distinct Regions of the Ventral Tegmental Area Differentially Modulates Mood-Related Behaviors
Bolaños, C. A., Perrotti, L. I., Edwards, S., Eisch, A. J., Barrot, M., Olson, V. G., Russell, D. S., Neve, R. L., & Nestler, E. J. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-20-07569.2003 · Cited by 62 · see citing works
“…previous studies that have demonstrated that topographical differences within the VTA mediate the rewarding and aversive properties of drugs (Ikemoto et al., 1997, 1998; Carlezon et al., 2000b; Olson et al., 2001), and we now extend these previous findings to a natural reward, namely sucrose.”
Influential
Efferent connections of the rostral linear nucleus of the ventral tegmental area in the rat
Del-Fava, F., Hasue, R. H., Ferreira, J. G. P., & Shammah-Lagnado, S. J. (2007) · Neuroscience · doi:10.1016/j.neuroscience.2006.12.039 · Cited by 56 · see citing works
Adeno-associated viral serotypes produce differing titers and differentially transduce neurons within the rat basal and lateral amygdala
Holehonnur, R., Luong, J. A., Chaturvedi, D., Ho, A., Lella, S. K., Hosek, M. P., & Ploski, J. E. (2014) · BMC Neuroscience · doi:10.1186/1471-2202-15-28 · Cited by 58 · see citing works
Rewarding Effects of AMPA Administration into the Supramammillary or Posterior Hypothalamic Nuclei But Not the Ventral Tegmental Area
Ikemoto, S., Witkin, B. M., Zangen, A., & Wise, R. A. (2004) · Journal of Neuroscience · doi:10.1523/jneurosci.5367-04.2004 · Cited by 56 · see citing works
Glutamate Mechanisms Underlying Opiate MemoriesPreprint
Peters, J., & Vries, T. J. D. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a012088 · Cited by 56 · see citing works
Effects of deletion of gria1 or gria2 genes encoding glutamatergic AMPA-receptor subunits on place preference conditioning in mice
Mead, A. N., Brown, G., Le Merrer, J., & Stephens, D. N. (2005) · Psychopharmacology · doi:10.1007/s00213-004-2071-8 · Cited by 52 · see citing works
Dopaminergic cellular and circuit contributions to kappa opioid receptor mediated aversion
Margolis, E. B., & Karkhanis, A. N. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.104504 · Cited by 51 · see citing works
“While most often studied in the context of positive reinforcement and reward, the dopaminergic neurons of the ventral tegmental area (VTA) have also long been implicated specifically in the processing of aversive experiences (Ableitner and Herz, 1989; Carlezon et al., 2000).”
Hippocampal GluA1-Containing AMPA Receptors Mediate Context-Dependent Sensitization to Morphine
Xia, Y., Portugal, G. S., Fakira, A. K., Melyan, Z., Neve, R. L., Lee, H. T., Russo, S. J., Liu, J., & Morón, J. A. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3835-11.2011 · Cited by 51 · see citing works
Glutamatergic Systems and Memory Mechanisms Underlying Opioid AddictionPreprint
Heinsbroek, J. A., Vries, T. J. D., & Peters, J. (2020) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a039602 · Cited by 49 · see citing works
Effects of social defeat on dopamine neurons in the ventral tegmental area in male and female California mice
Greenberg, G. D., Steinman, M. Q., Doig, I. E., Hao, R., & Trainor, B. C. (2015) · European Journal of Neuroscience · doi:10.1111/ejn.13099 · Cited by 49 · see citing works
“Coronal sections have been used to examine rostral vs. caudal topography in anatomical (Carlezon et al., 2000) and functional (Mahler & Aston-Jones, 2012) analyses.”
BackgroundMethod
Place Conditioning to Study Drug Reward and Aversion
Carlezon, W. A. (2003) · Humana Press eBooks · doi:10.1385/1-59259-379-8:243 · Cited by 48 · see citing works
Ventral tegmental area glutamate neurons establish a mu-opioid receptor gated circuit to mesolimbic dopamine neurons and regulate opioid-seeking behavior
McGovern, D. J., Polter, A. M., Prévost, E. D., Ly, A., McNulty, C. J., Rubinstein, B., & Root, D. H. (2023) · Neuropsychopharmacology · doi:10.1038/s41386-023-01637-w · Cited by 49 · see citing works
“E Mg/kg oxycodone consumption for females.”
The Reinforcing Actions of a Serotonin-3 Receptor Agonist within the Ventral Tegmental Area: Evidence for Subregional and Genetic Differences and Involvement of Dopamine Neurons
Rodd, Z. A., Gryszowka, V. E., Toalston, J. E., Oster, S. M., Ji, D., Bell, R. L., & McBride, W. J. (2007) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1124/jpet.106.112607 · Cited by 43 · see citing works
“Overexpression of an -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor subunit (GluR1) in the posterior and anterior VTA produced differential consequences on morphine-conditioned place preference (Carlezon et al., 2000).”
Background
Motor skill learning and reward consumption differentially affect VTA activation
Leemburg, S., Canonica, T., & Luft, A. R. (2018) · Scientific Reports · doi:10.1038/s41598-017-18716-w · Cited by 38 · see citing works
Repeated Exposure to Rewarding Brain Stimulation Downregulates GluR1 Expression in the Ventral Tegmental Area
Carlezon, W. A. (2001) · Neuropsychopharmacology · doi:10.1016/s0893-133x(01)00232-9 · Cited by 41 · see citing works
“…in GluR1 expression in the rostral VTA (the predominant region probed in the present studies) by viral-mediated gene transfer can increase responsivity to the rewarding effects of morphine (Carlezon et al. 1997, 2000), establishing causal relations between ele- N EUROPSYCHOPHARMACOLOGY 2001 – VOL .”
Background
Viral vector approaches to modify gene expression in the brain
Papale, A., Cerovic, M., & Brambilla, R. (2009) · Journal of Neuroscience Methods · doi:10.1016/j.jneumeth.2009.08.013 · Cited by 39 · see citing works
Individual Differences in Nucleus Accumbens Dopamine Receptors Predict Development of Addiction-Like Behavior: A Computational Approach
Piray, P., Keramati, M., Dezfouli, A., Lucas, C., & Mokri, A. (2010) · Neural Computation · doi:10.1162/neco_a_00009 · Cited by 39 · see citing works
“…the VTA is important for mediating the rewarding effects of many drugs such as cocaine, nicotine, carbachol, cannabinoids, ethanol, and opiates (Carlezon et al., 1997, 2000; Ford et al., 2006; Ikemoto, Murphy, & McBride, 1998; Ikemoto et al., 1997; Ikemoto & Wise, 2002; Rodd et al., 2004,…”
Blockade of ionotropic glutamatergic transmission in the ventral tegmental area attenuates the physical signs of morphine withdrawal in rats
Wang, H., Zhao, Y., Xiang, X., Wang, H., & Wu, W.-R. (2004) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2004.05.043 · Cited by 38 · see citing works
Excitatory Synaptic Function and Plasticity is Persistently Altered in Ventral Tegmental Area Dopamine Neurons after Prenatal Ethanol Exposure
Hausknecht, K. A., Haj‐Dahmane, S., Shen, Y.-L., Vezina, P., Dlugos, C. A., & Shen, R. (2014) · Neuropsychopharmacology · doi:10.1038/npp.2014.265 · Cited by 37 · see citing works
Prenatal Ethanol Exposure Persistently Alters Endocannabinoid Signaling and Endocannabinoid-Mediated Excitatory Synaptic Plasticity in Ventral Tegmental Area Dopamine Neurons
Hausknecht, K. A., Shen, Y.-L., Wang, R., Haj‐Dahmane, S., & Shen, R. (2017) · Journal of Neuroscience · doi:10.1523/jneurosci.3894-16.2017 · Cited by 32 · see citing works
Pituitary Adenylate Cyclase-Activating Peptide (PACAP) Signaling and the Dark Side of Addiction
Miles, O. W., May, V., & Hammack, S. E. (2018) · Journal of Molecular Neuroscience · doi:10.1007/s12031-018-1147-6 · Cited by 33 · see citing works
Prenatal Stress Exposure Increases the Excitation of Dopamine Neurons in the Ventral Tegmental Area and Alters Their Reponses to Psychostimulants
Hausknecht, K. A., Haj‐Dahmane, S., & Shen, R. (2012) · Neuropsychopharmacology · doi:10.1038/npp.2012.168 · Cited by 32 · see citing works
Anterior and posterior parts of the rat ventral tegmental area and the rostromedial tegmental nucleus receive topographically distinct afferents from the lateral habenular complex
Petzel, A., Bernard, R., Poller, W. C., & Veh, R. W. (2017) · The Journal of Comparative Neurology · doi:10.1002/cne.24200 · Cited by 31 · see citing works
“, 1997), and became generally accepted (Carlezon et al., 2000; Olson et al., 2005; Rodd-Henricks et al., 2000; ShabatSimon et al., 2008).”
BackgroundInfluential
Insulin receptor substrate-2 in the ventral tegmental area regulates behavioral responses to cocaine.
Iñiguez, S. D., Warren, B. L., Neve, R. L., Nestler, E. J., Russo, S. J., & Bolaños‐Guzmán, C. A. (2008) · Behavioral Neuroscience · doi:10.1037/a0012893 · Cited by 31 · see citing works
“…mediate differential responding to the rewarding and locomotor-activating properties of drugs (Bolaños, Neve, & Nestler, 2005; Bolaños et al., 2003; Carlezon et al., 2000; Ikemoto, Kohl, & McBride, 1997; Olson et al., 2005), it is conceivable that distinct populations of dopamine neurons within…”
Prenatal ethanol exposure increases risk of psychostimulant addiction
Wang, R., Shen, Y.-L., Hausknecht, K. A., Chang, L., Haj‐Dahmane, S., Vezina, P., & Shen, R. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.07.030 · Cited by 30 · see citing works
NMDA Receptor Blockade in the Prelimbic Cortex Activates the Mesolimbic System and Dopamine-Dependent Opiate Reward Signaling
Tan, H., Rosen, L. G., Ng, G. A., Rushlow, W. J., & Laviolette, S. R. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3616-0 · Cited by 28 · see citing works
Viral-mediated expression of extracellular signal-regulated kinase-2 in the ventral tegmental area modulates behavioral responses to cocaine
Iñiguez, S. D., Warren, B. L., Neve, R. L., Russo, S. J., Nestler, E. J., & Bolaños‐Guzmán, C. A. (2010) · Behavioural Brain Research · doi:10.1016/j.bbr.2010.05.040 · Cited by 27 · see citing works
Morphine induction of c-fos expression in the rat forebrain through glutamatergic mechanisms: role of non-n-methyl-d-aspartate receptors
Garcia, M. M., Anderson, A. T., Edwards, R., & Harlan, R. E. (2003) · Neuroscience · doi:10.1016/s0306-4522(02)00975-2 · Cited by 26 · see citing works
The production of viral vectors designed to express large and difficult to express transgenes within neurons
Holehonnur, R., Lella, S. K., Ho, A., Luong, J. A., & Ploski, J. E. (2015) · Molecular Brain · doi:10.1186/s13041-015-0100-7 · Cited by 25 · see citing works
“Viral vectors have become a common tool in neuroscience to express transgenes in a spatially and temporally restricted manner within the nervous system of numerous model organisms [1-5].”
Background
Ionotropic glutamatergic neurotransmission in the ventral tegmental area modulates ΔFosB expression in the nucleus accumbens and abstinence syndrome in morphine withdrawal rats
Wang, H., Xiang, X., Guo, Y., Wu, W.-R., Cao, D., Wang, H., & Zhao, Y. (2005) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2005.10.017 · Cited by 24 · see citing works
Endomorphin‐1 and ‐2 immunoreactive cells in the hypothalamus are labeled by fluoro‐gold injections to the ventral tegmental area
Greenwell, T. N., Zangen, A., Martin‐Schild, S., Wise, R. A., & Zadina, J. E. (2002) · The Journal of Comparative Neurology · doi:10.1002/cne.10464 · Cited by 24 · see citing works
“When the AMPA glutamate receptor subunit GluR1 is overexpressed in the anterior VTA, the rewarding effects of morphine are enhanced, whereas overexpression in the posterior VTA produces aversive responses to morphine (Carlezon et al., 2000).”
Background
Use of Adeno‐Associated and Herpes Simplex Viral Vectors for In Vivo Neuronal Expression in Mice
Penrod, R. D., Wells, A. M., Carlezon, W. A., & Cowan, C. W. (2015) · Current Protocols in Neuroscience · doi:10.1002/0471142301.ns0437s73 · Cited by 22 · see citing works
“…applications for HSV vector systems are broad and include gene overexpression (Carlezon et al., 1997; Carlezon et al., 1998; Kelz et al., 1999; Carlezon et al., 2000; Pliakas et al., 2001; Rumpel et al., 2005; Gräff et al., 2014; Scobie et al., 2014), mutations resulting in loss of function…”
Background
Effects of psychotropic drugs on second messenger signaling and preference for nicotine in juvenile male mice
Parise, L. F., Warren, B. L., Parise, E. M., Iñiguez, S. D., & Bolaños‐Guzmán, C. A. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3434-4 · Cited by 22 · see citing works
Effects of Psychomotor Stimulants on Glutamate Receptor Expression
Wolf, M. E. (2003) · Humana Press eBooks · doi:10.1385/1-59259-358-5:13 · Cited by 22 · see citing works
“Another fi nding relevant to this controversy is that overexpression of GluR1 in the rostral VTA using a herpes simplex virus resulted in intensifi cation of the locomotor stimulant and rewarding properties of morphine (16,17).”
Background
The vesicular glutamate transporter-1 upstream promoter and first intron each support glutamatergic-specific expression in rat postrhinal cortex
Zhang, G., Xu, L., Cao, H., Zhao, H. Y., & Geller, A. I. (2010) · Brain Research · doi:10.1016/j.brainres.2010.12.040 · Cited by 20 · see citing works
Differential effects of dopamine D2 and GABAA receptor antagonists on dopamine neurons between the anterior and posterior ventral tegmental area of female Wistar rats
Ding, Z., Liu, W., Engleman, E. A., Rodd, Z. A., & McBride, W. J. (2009) · Pharmacology Biochemistry and Behavior · doi:10.1016/j.pbb.2009.01.004 · Cited by 19 · see citing works
“Over-expression of either one of the GluR1 subunit of the AMPA receptor, phospholipase Cγ subunit, or cAMP-response element -binding protein in the anterior VTA enhanced the rewarding effects of morphine and cocaine, whereas the same manipulations in the posterior VTA caused aversion to morphine and cocaine (Bolanos e…”
Background
Topographical Fos induction within the ventral midbrain and projection sites following self-stimulation of the posterior mesencephalon
Marcangione, C., & Rompré, P.-P. (2008) · Neuroscience · doi:10.1016/j.neuroscience.2008.05.014 · Cited by 16 · see citing works
Decreased sensitivity to the effects of dopamine D1-like, but not D2-like, receptor antagonism in the posterior hypothalamic region/anterior ventral tegmental area on brain reward function during chronic exposure to nicotine in rats
Bruijnzeel, A. W., & Markou, A. (2005) · Brain Research · doi:10.1016/j.brainres.2005.07.056 · Cited by 17 · see citing works
Brain stimulation rewarding experience attenuates neonatal clomipramine-induced adulthood anxiety by reversal of pathological changes in the amygdala
Chakraborty, S., Tripathi, S. J., Raju, T. R., & Rao, B. S. S. (2020) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2020.110000 · Cited by 15 · see citing works
Virogenetic and optogenetic mechanisms to define potential therapeutic targets in psychiatric disorders
Han, M., & Friedman, A. K. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.09.009 · Cited by 15 · see citing works
“Surprisingly, morphine is both rewarding and aversive when GluR1 is virally expressed in the rostral and caudal VTA, respectively (Carlezon et al., 2000a).”
Background
Phospholipase Cγ in distinct regions of the ventral tegmental area differentially regulates morphine‐induced locomotor activity
Bolaños, C. A., Neve, R. L., & Nestler, E. J. (2005) · Synapse · doi:10.1002/syn.20136 · Cited by 15 · see citing works
Toward a Developmental Psychopathology of Personality Disturbance: A Neurobehavioral Dimensional Model
Depue, R. A., & Lenzenweger, M. F. (2015) · Wiley eBooks · doi:10.1002/9780470939390.ch20 · Cited by 12 · see citing works
Unconditional hyperactivity and transient reinforcing effects of NMDA administration into the ventral tegmental area in rats
Ikemoto, S. (2004) · Psychopharmacology · doi:10.1007/s00213-003-1651-3 · Cited by 11 · see citing works
“Functional heterogeneity like that of the VTA has also been found in other neurochemical systems (Carlezon et al. 2000; RoddHenricks et al. 2000; Boehm et al. 2002; Ikemoto and Wise 2002; Zangen et al. 2002).”
Background
The Dynorphin/-Opioid Receptor System at the Interface of Hyperalgesia/Hyperkatifeia and Addiction
Marchette, R. C. N., Vendruscolo, L. F., & Koob, G. F. (2025) · Current Addiction Reports · doi:10.1007/s40429-025-00618-x · Cited by 13 · see citing works
“The reduction of dopamine release caused by dynor-phin, particularly in the nucleus accumbens shell, was also hypothesized to modulate aversive/rewarding aspects of drug intake [147].”
Post-translational modification of cortical GluA receptors in rodents following spinal cord lesion
Li, J., Voulalas, P. J., Ji, Y., & Masri, R. M. (2015) · Neuroscience · doi:10.1016/j.neuroscience.2015.12.038 · Cited by 9 · see citing works
“…after viral injection and reaching maximal expression 2–5 days post-injection, before diminishing to undetectable levels 8–10 days after injection (Carlezon et al., 2000b; Carlezon et al., 2000a; Choi et al., 2003; Neve et al., 2005; Todtenkopf et al., 2006; Bachtell et al., 2008; Hobson et…”
Background
Application of adeno-associated viral vectors in behavioral research
Nair, H. P., & Young, L. J. (2002) · Methods · doi:10.1016/s1046-2023(02)00223-2 · Cited by 8 · see citing works
Differential patterns of neuronal activation in rostral versus caudal ventral tegmental area involved in behavioral sensitization induced by an escalating-dose morphine administration paradigm
Bai, Y., Peng, Y.-H., Liang, J., & Zheng, X. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.05.011 · Cited by 7 · see citing works
“…because functional differences in the rostral vs. caudal VTA have been reported (Arnt and Scheel-Kruger, 1979; Ikemoto et al., 1997, 1998), and the rostral rather than caudal VTA appears to be responsible for the increased sensitivity to morphine (Bolanos et al., 2005; Carlezon et al., 1997, 2000).”
Influential
Glycogen synthase kinase-3β in the ventral tegmental area mediates diurnal variations in cocaine-induced conditioned place preference in rats
Li, S., Wei, Y.-M., Shi, H., Luo, Y., Ding, Z., Xue, Y.-X., Lü, L., & Yu, C. (2013) · Addiction Biology · doi:10.1111/adb.12068 · Cited by 4 · see citing works
“Previous study (Carlezon et al. 2000; Olson et al. 2008) showed that the VTA is a heterogeneous brain region, with at least two functionally discrete subregions (i.”
Background
Molecular Mechanisms of Opioid Dependence by Using Knockout Mice
Kieffer, B. L., & Simonin, F. (2003) · Humana Press eBooks · doi:10.1007/978-1-59259-343-9_1 · Cited by 3 · see citing works
7.2 Dopamine and Synaptic Plasticity in Mesolimbic Circuits
Hopf, F. W., Bonci, A., & Malenka, R. C. (2009) · doi:10.1093/acprof:oso/9780195373035.003.0024
Ventral Tegmental Area Regulation Of Stress-Induced Reinstatement Of Cocaine-Seeking Behavior
Blacktop, J. M. (2014) · e-Publications@Marquette (Marquette University)
Morphine-induced Locomotion Increases following Viral Transfection of M5 Muscarinic Receptor Genes in the Ventromedial Hypothalamus of Wild-type Mice
Nawaz, S. (2011) · TSpace (University of Toronto)
The Role of Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) in the Neurobiology of Stress-Related Behaviors
Donahue, R. J. (2016) · Digital Access to Scholarship at Harvard (DASH) (Harvard University)
Intra-cellular mechanisms by which PAC1 receptor activation mediates stress-induced reinstatement to drug-seeking
Miles, O. W. (2018) · ScholarWorks -A service of University of Vermont Libraries (University of Vermont)

Region-Specific Changes in the Subcellular Distribution of AMPA Receptor GluR1 Subunit in the Rat Ventral Tegmental Area after Acute or Chronic Morphine Administration
Lane, D., Lessard, A., Chan, J., Colago, E. E. O., Zhou, Y., Schlussman, S. D., Kreek, M. J., & Pickel, V. M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.2151-08.2008 · Cited by 56 · see citing works
Sensitization to Morphine Induced by Viral-Mediated Gene Transfer
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Reinforcing effects of morphine microinjection into the ventral tegmental area
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Brain Regional Fos Expression Elicited by the Activation of μ- but not δ-Opioid Receptors of the Ventral Tegmental Area: Evidence for an Implication of the Ventral Thalamus in Opiate Reward
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Different effects of GABAergic receptors located in the ventral tegmental area (VTA) on the expression of morphine-induced conditioned place preference in rat
Sahraei, H., Amiri, Y.-A., Rohani, A. H., & Sepehri, H. (2002) · European Neuropsychopharmacology · doi:10.1016/s0924-977x(02)80639-3

Authors: Carlezon, W. A., Haile, C. N., Coppersmith, R., Hayashi, Y., Malinow, R., Neve, R. L., & Nestler, E. J.
Affiliations: Yale University (US)
Harvard University (US)
Cold Spring Harbor Laboratory (US)
McLean Hospital (US)
ORCID: Carlezon, William A.
Haile, Colin N.
Hayashi, Yasunori
Malinow, Roberto
Neve, Rachael L.
Nestler, Eric J.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2000-03-01
Volume: 20
Issue: 5
Pages: RC62-RC62
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.20-05-j0002.2000
PMC: PMC6772915
OpenAlex: W1781339509
Cited by: 98
References: 22
Citations by year: 2025: 1 · 2023: 1 · 2020: 2 · 2019: 1 · 2018: 4 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 7 · 2013: 1 · 2012: 6
FWCI: 2.59
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 184 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
Funders: National Institute of Mental Health
National Institute on Drug Abuse (DA 08227, DA07359, DA05758, P01DA008227)
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: morphine, opioid reward, ventral tegmental area, GluR1, AMPA receptors, herpes simplex virus vectors, conditioned place preference, dopaminergic neurons, midbrain
MeSH terms: Animals, Conditioning, Operant, Genetic Vectors, Male, Microinjections, Morphine, Narcotics, Reward, Rats, Sprague-Dawley, Ventral Tegmental Area, Receptors, AMPA, Simplexvirus, Microscopy, Confocal, Rats

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Distinct sites of opiate reward and aversion within the midbrain identified using a herpes simplex virus vector expressing GluR1

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