title: Prolonged nicotine exposure does not alter GABA(B) receptor-mediated regulation of brain reward function.
abstract: Gamma-aminobutyric acid subtype B (GABA(B)) receptors play an important role in regulating brain reward function. Accumulating evidence suggests that chronic exposure to drugs of abuse may alter GABA(B) 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 GABA(B) 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 gamma-vinyl-GABA or the GABA(B) 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 GABA(B) receptor-mediated regulation of brain reward function, and suggest that alterations in GABA(B) receptor activity are unlikely to play a role in the brain reward deficits associated with spontaneous nicotine withdrawal.
authors: Department of Molecular and Integrative Neuroscience, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
authors: Neil E
authors: NE
authors: Paterson
authors: Adrie W
authors: AW
authors: Bruijnzeel
authors: Paul J
authors: PJ
authors: Kenny
authors: Cory D
authors: CD
authors: Wright
authors: Wolfgang
authors: W
authors: Froestl
authors: Athina
authors: A
authors: Markou
mesh_terms: D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000818:Animals; D001921:Brain / Q000502:physiology*; D004298:Dopamine / Q000502:physiology; D004567:Electrodes, Implanted; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D008032:Limbic System / Q000187:drug effects / Q000502:physiology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D018080:Receptors, GABA-B / Q000187:drug effects*; D012201:Reward; D012653:Self Stimulation; D009435:Synaptic Transmission / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000502:physiology; D020888:Vigabatrin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018755:GABA Agonists; D058786:GABA-B Receptor Agonists; D018722:Nicotinic Agonists; D018080:Receptors, GABA-B; D009538:Nicotine; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D004298:Dopamine