Prolonged nicotine exposure does not alter GABAB receptor-mediated regulation of brain reward function

γ-Aminobutyric acid subtype B (GABAB) receptors play an important role in regulating brain reward function. Accumulating evidence suggests that chronic exposure to drugs of abuse may alter GABAB receptor function. The present studies investigated whether chronic nicotine administration, using a regimen that induces nicotine dependence, increased inhibitory regulation of brain reward function by GABAB receptors, as measured by intracranial self-stimulation (ICSS) thresholds in rats. Such an action of nicotine may contribute to the reward deficit observed during nicotine withdrawal. Nicotine-dependent and control rats received the GABA transaminase inhibitor γ-vinyl-GABA or the GABAB receptor agonist CGP44532 according to a within-subjects Latin square design, and ICSS thresholds were assessed post-injection. Systemic administration of the lowest doses of GVG or CGP44532 did not alter reward thresholds in control or nicotine-treated rats, whereas the highest doses of each drug elevated thresholds similarly in both groups. Further, micro-infusion of CGP44532 directly into the ventral tegmental area elevated ICSS thresholds similarly in saline- and nicotine-treated rats. Overall, these data demonstrate that prolonged nicotine exposure did not alter GABAB receptor-mediated regulation of brain reward function, and suggest that alterations in GABAB receptor activity are unlikely to play a role in the brain reward deficits associated with spontaneous nicotine withdrawal.