Differential role of N-methyl-D-aspartate receptor-mediated glutamate transmission in the nucleus accumbens shell and core in nicotine seeking in rats.
Nicotine, a major psychoactive component of tobacco smoke, increases glutamate transmission in the nucleus accumbens (NAcc). However, the role of the N-methyl-D-aspartate (NMDA)-mediated glutamatergic neurotransmission in the NAcc shell and core subdivisions in nicotine-dependent behaviors has not been studied. The present study evaluated, in rats, the effects of bilateral administration of the competitive NMDA receptor antagonist LY235959 (0, 0.1, 1, and 10 ng/0.5 μL/side) into the NAcc shell or core on intravenous nicotine (fixed- and progressive-ratio schedules) and food (fixed-ratio schedule) self-administration, and cue-induced reinstatement of nicotine-seeking behavior. In addition, the effects of LY235959 injections in the NAcc shell were evaluated on nicotine-induced conditioned taste aversion, a procedure that assesses the aversive effects of nicotine. LY235959 injections into the NAcc shell significantly increased nicotine self-administration under both fixed- and progressive-ratio schedules, and decreased food self-administration, but had no effect on nicotine-induced conditioned taste aversion or cue-induced nicotine seeking. Furthermore, injections of LY235959 in the lateral septal nucleus, originally intended as an anatomical control site for the NAcc shell, increased nicotine self-administration and decreased food self-administration under the fixed-ratio schedule. In contrast, LY235959 injections into the NAcc core increased the cue-induced reinstatement of nicotine seeking and decreased food self-administration, but had no effect on nicotine self-administration. The present data suggest that NMDA receptor-mediated glutamatergic neurotransmission in the NAcc shell and core differentially regulates food- and nicotine-maintained responding. Importantly, the data suggest an inhibitory role for NMDA-mediated glutamatergic neurotransmission in the NAcc shell and core in nicotine self-administration and the cue-induced reinstatement of nicotine seeking, respectively.
Department of Psychiatry, M/C 0603, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA, 92093-0603, USA.
Manoranjan S
MS
D'Souza
Athina
A
Markou
D000818:Animals; D058999:Drug-Seeking Behavior; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012646:Self Administration; D009435:Synaptic Transmission
D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D009538:Nicotine; C088643:LY 235959
aversion; glutamate receptors; motivation; nucleus accumbens; progressive ratio; reward