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.