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Differential involvement of ventral tegmental GABA(A) and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress.
Brain Res. 2007 May 30; 1150:62-8.BR

Abstract

Evidence indicates that dopamine (DA) transmission in nucleus accumbens (NAcc) is modulated by glutamate (GLUT) projections from medial prefrontal cortex (PFC) to NAcc and the ventral tegmental area (VTA). Local NMDA receptor blockade in NAcc has previously been shown to enhance the DA stress response in this region as well as in the VTA. This raises the possibility that the NAcc DA stress response is regulated by GLUT acting at NMDA receptors located on NAcc GABA output neurons that project to the VTA where GABA is known to regulate DA cell activity. Thus, in the present study, we used voltammetry to examine the effects of intra-VTA administration of GABA(A) and GABA(B) agonists and antagonists on restraint stress-induced increases in NAcc DA. The results show that local VTA GABA(B) receptor activation with baclofen (0.01, 0.1 and 1.0 nmol) dose-dependently inhibited the NAcc DA stress response whereas GABA(B) receptor blockade with phaclofen had the opposite effect, resulting in a dose-dependent potentiation of the stress response. A similar potentiation of the NAcc DA stress response was observed following VTA GABA(A) receptor blockade with bicuculline, but only at the highest dose (1.0 nmol). Interestingly, intra-VTA injection of the GABA(A) receptor agonist, muscimol, at the lowest dose (0.01 nmol) but not at the higher doses (0.1 or 1.0 nmol) also potentiated the NAcc DA stress response, suggesting an action mediated primarily at GABA(A) receptors located on non-DA neurons. These results indicate that the NAcc DA stress response is regulated by GABA afferents to VTA DA cells and that this action is differentially mediated by GABA(A) and GABA(B) receptors. The data suggest that the relevant GABA(B) receptors are located on DA neurons whereas the GABA(A) receptors are located on GABA interneurons and perhaps also on DA cells. The present findings are also consistent with the idea that the corticofugal GLUT input to NAcc indirectly regulates stress-induced DA release in this region through the GABA feedback pathway to VTA.

Authors+Show Affiliations

Douglas Hospital Research Center, Department of Psychiatry, McGill University, 6875 LaSalle Blvd, Montréal Verdun, Québec, Canada, H4H 1R3.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17395162

Citation

Doherty, Michael, and Alain Gratton. "Differential Involvement of Ventral Tegmental GABA(A) and GABA(B) Receptors in the Regulation of the Nucleus Accumbens Dopamine Response to Stress." Brain Research, vol. 1150, 2007, pp. 62-8.
Doherty M, Gratton A. Differential involvement of ventral tegmental GABA(A) and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. Brain Res. 2007;1150:62-8.
Doherty, M., & Gratton, A. (2007). Differential involvement of ventral tegmental GABA(A) and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. Brain Research, 1150, 62-8.
Doherty M, Gratton A. Differential Involvement of Ventral Tegmental GABA(A) and GABA(B) Receptors in the Regulation of the Nucleus Accumbens Dopamine Response to Stress. Brain Res. 2007 May 30;1150:62-8. PubMed PMID: 17395162.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Differential involvement of ventral tegmental GABA(A) and GABA(B) receptors in the regulation of the nucleus accumbens dopamine response to stress. AU - Doherty,Michael, AU - Gratton,Alain, Y1 - 2007/03/06/ PY - 2006/09/29/received PY - 2007/02/20/revised PY - 2007/02/23/accepted PY - 2007/3/31/pubmed PY - 2007/7/25/medline PY - 2007/3/31/entrez SP - 62 EP - 8 JF - Brain research JO - Brain Res. VL - 1150 N2 - Evidence indicates that dopamine (DA) transmission in nucleus accumbens (NAcc) is modulated by glutamate (GLUT) projections from medial prefrontal cortex (PFC) to NAcc and the ventral tegmental area (VTA). Local NMDA receptor blockade in NAcc has previously been shown to enhance the DA stress response in this region as well as in the VTA. This raises the possibility that the NAcc DA stress response is regulated by GLUT acting at NMDA receptors located on NAcc GABA output neurons that project to the VTA where GABA is known to regulate DA cell activity. Thus, in the present study, we used voltammetry to examine the effects of intra-VTA administration of GABA(A) and GABA(B) agonists and antagonists on restraint stress-induced increases in NAcc DA. The results show that local VTA GABA(B) receptor activation with baclofen (0.01, 0.1 and 1.0 nmol) dose-dependently inhibited the NAcc DA stress response whereas GABA(B) receptor blockade with phaclofen had the opposite effect, resulting in a dose-dependent potentiation of the stress response. A similar potentiation of the NAcc DA stress response was observed following VTA GABA(A) receptor blockade with bicuculline, but only at the highest dose (1.0 nmol). Interestingly, intra-VTA injection of the GABA(A) receptor agonist, muscimol, at the lowest dose (0.01 nmol) but not at the higher doses (0.1 or 1.0 nmol) also potentiated the NAcc DA stress response, suggesting an action mediated primarily at GABA(A) receptors located on non-DA neurons. These results indicate that the NAcc DA stress response is regulated by GABA afferents to VTA DA cells and that this action is differentially mediated by GABA(A) and GABA(B) receptors. The data suggest that the relevant GABA(B) receptors are located on DA neurons whereas the GABA(A) receptors are located on GABA interneurons and perhaps also on DA cells. The present findings are also consistent with the idea that the corticofugal GLUT input to NAcc indirectly regulates stress-induced DA release in this region through the GABA feedback pathway to VTA. SN - 0006-8993 UR - https://www.unboundmedicine.com/medline/citation/17395162/Differential_involvement_of_ventral_tegmental_GABA_A__and_GABA_B__receptors_in_the_regulation_of_the_nucleus_accumbens_dopamine_response_to_stress_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(07)00512-4 DB - PRIME DP - Unbound Medicine ER -