Camp MC, Alcantara AA (2007) Cholinergic saporin lesions in the nucleus accumbens attenuate alcohol drinking. Neuroscience 2007 Abstracts 809.4/X26. Society for Neuroscience, San Diego, CA.
Summary: Identifying specific cell types and the plasticity that occurs within those neuronal networks that lead to alcohol drinking is critical for the development of improved treatment programs for alcoholism. We have previously reported that cholinergic neurons of the nucleus accumbens (NAc) undergo alcohol-induced intracellular and receptor neuroadaptations. These changes may facilitate acetylcholine (ACh) release, which in turn modulate the neuronal circuits that underlie alcohol drinking. We postulate that alcohol-induced neuroplasticity of the cholinergic system facilitates alcohol drinking whereas removal of ACh influences attenuates alcohol drinking. Cholinergic cell lesion studies investigating a direct causal role of these neurons in drug abuse and memory have reported their importance in reinforcement, conditioned place preference, reward-related procedural learning and working memory. The effects of accumbal cholinergic lesions on alcohol drinking, however, have not been examined. To test a direct causal link between cholinergic cells and alcohol drinking, the present study employed bilateral cholinergic cell lesions in the NAc and measured alcohol drinking in C57BL/6J mice. The effects of cholinergic ablation on alcohol drinking were examined following a Drinking in the Dark model of binge drinking and on motor impairment using the fixed speed rotarod test. Cholinergic ablations were produced by microinjections of mu p75-saporin into the NAc. After recovery, animals were given 20% (v/v) ethanol in water for 4 hours a day in the home cage starting 3 hours after lights off for 1 month. Cholinergic cell eliminated mice showed a 26% decrease in alcohol drinking compared to saline microinjected controls (p<0.05) and fell from the rotarod 24% sooner than controls (p<0.05). The present study provides evidence of a direct causal link between cholinergic cells and alcohol drinking. These results suggest that increased ACh release facilitates binge drinking, whereas removal of ACh signaling attenuates drinking. These findings provide the basis for accumbal cholinergic-targeted pharmaceutical and behavioral treatment programs designed to attenuate alcohol binge drinking.
Related Products: mu p75-SAP (Cat. #IT-16)