title: The role of nucleus accumbens shell GABA receptors on ventral tegmental area intracranial self-stimulation and a potential role for the 5-HT(2C) receptor.
abstract: Brain γ-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT)(2C) receptors are implicated in the neuronal regulation of reward- and aversion-related behaviour. Within the mesocorticolimbic pathways of the brain, relationships between GABA containing neurons and 5-HT(2C) receptor activity may be important in this context. The primary aim of this study was to investigate the role of NAc shell GABA receptors on ventral tegmental area intracranial self-stimulation (ICSS) and to examine the systemic effects of GABAergic ligands in this context. The second aim was to investigate the relationship between GABA receptor- and 5-HT(2C) receptor-related ICSS behaviour, using systemic administration of the selective agonist WAY 161503. Locomotor activity was assessed to compare the potential motor effects of drugs; feeding behaviour and intra-NAc injections of amphetamine (1.0 µg/side) were used as positive controls. When administered systemically the GABA(A) receptor agonist muscimol and antagonist picrotoxin did not selectively change ICSS reward thresholds, although the 5-HT(2C) receptor agonist WAY 161503 (1.0 mg/kg) decreased reward measures. Intra-NAc shell administration of muscimol (225 ng/side) and picrotoxin (125 ng/side), respectively, decreased and increased measures of reward. Intra-NAc shell baclofen (0-225 ng/side; GABA(B) receptor agonist) did not affect any ICSS measures although it increased feeding. Combining picrotoxin and WAY 161503 attenuated the effects of each. These results suggest that a 5-HT(2C) and GABA(A) receptor-mediated neuronal relationship in the NAc shell may be relevant for the regulation of brain reward pathways.
authors.affiliation: Centre for Neuroscience, University of Alberta, Edmonton, AB, Canada. david.hayes@rohcg.on.ca
authors.forename: Dave J
authors.initials: DJ
authors.lastname: Hayes
authors.forename: John
authors.initials: J
authors.lastname: Hoang
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Greenshaw
mesh_terms: D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009118:Muscimol / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000502:physiology*; D011719:Pyrazines / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044405:Receptor, Serotonin, 5-HT2C / Q000502:physiology*; D018079:Receptors, GABA / Q000502:physiology*; D012653:Self Stimulation; D017557:Ventral Tegmental Area / Q000502:physiology*
chemical_list: C502777:8,9-dichloro-2,3,4,4a-tetrahydro-1H-pyrazino(1,2-a)quinoxalin-5(6H)-one; D011719:Pyrazines; D011810:Quinoxalines; D044405:Receptor, Serotonin, 5-HT2C; D018079:Receptors, GABA; D009118:Muscimol; D001418:Baclofen