Effect of CB1 receptor blockade on food-reinforced responding and associated nucleus accumbens neuronal activity in rats.
Studies have shown that disruption of cannabinoid receptor signaling reduces operant responses for rewards; yet it is unknown whether changes in neural activity at dopamine terminal regions such as the nucleus accumbens (NAc) underlie these behavioral effects. To study the neural correlates that accompany the disruption of endogenous cannabinoid (eCB) signaling in a food-motivated task, we recorded the neural activity and local field potentials (LFPs) from the NAc. A within-subject design was used for recordings as rats engaged in lever-pressing behavior for sucrose chocolate-flavored pellets delivered during responding in a progressive ratio (PR) schedule of reinforcement. Rats were food restricted to 85 ± 5% of their free body weight and trained under a PR until a stable breakpoint was observed (12 sessions ± 3). Once performance was stable, recordings were made under baseline, vehicle, and following administration of the cannabinoid inverse agonist rimonabant (150 μg/kg, i.v). NAc neurons encoded reward-predictive cues as well as food reward delivery. Rimonabant administration robustly reduced breakpoints in all rats tested, as previously reported. We found that this reduction is accompanied by a profound attenuation in the strength and coordination of specific event-related spiking activity. Moreover, rimonabant decreased LFP gamma power at 80 Hz (high gamma) at reward delivery and gamma power at 50 Hz (low gamma) at cue onset. Together the present results indicate that the eCB system sculpts neural activity patterns that accompany PR performance and reward consumption.
Department of Anatomy and Neurobiology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. giovannih{at}gmail.com
Giovanni
G
Hernandez
Joseph F
JF
Cheer
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D058256:Brain Waves / Q000187:drug effects / Q000502:physiology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology*; D003463:Cues; D004569:Electroencephalography; D005502:Food; D008297:Male; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects; D010880:Piperidines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012055:Reinforcement Schedule; D012054:Reinforcement, Psychology; D000077285:Rimonabant; D013057:Spectrum Analysis
D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D000077285:Rimonabant