The activity-regulated cytoskeleton-associated protein, Arc/Arg3.1, influences mouse cocaine self-administration

Publication date: Available online 1 November 2019Source: Pharmacology Biochemistry and BehaviorAuthor(s): Rachel D. Penrod, Morgane Thomsen, Makoto Taniguchi, Yuhong Guo, Christopher W. Cowan, Laura N. SmithAbstractThe activity-regulated cytoskeleton-associated protein (Arc, also known as Arg3.1), an immediate early gene and synaptic regulator, is upregulated following a single cocaine exposure. However, there is not much known regarding Arc/Arg3.1's potential contribution to addiction-relevant behaviors. Despite known learning and memory deficits in contextual fear and water-maze reversal learning tasks, we find that mice lacking Arc/Arg3.1 perform conditioned place preference and operant conditioning involving positive reinforcers (food and cocaine) with little-to-no impairment. Specifically, Arc/Arg3.1 KO mice show a mild impairment early in the acquisition of cocaine intravenous self-administration (IVSA). However, following normal saline-extinction, WT mice show a classic inverted-U dose-response function, while Arc/Arg3.1 KO mice fail to adjust their intake across multiple doses. Importantly, Arc/Arg3.1 KO and WT mice behave comparably on an increasing cost task (FR1-FR3; acquisition dose), providing evidence that both groups find cocaine reinforcing. Differences in individuals that drive variations in use patterns and particularly, drug intake levels, are critical as they influence the likelihood of developing dependence. Our data suggest that Arc/Arg3.1 may contribut...
Source: Pharmacology Biochemistry and Behavior - Category: Biochemistry Source Type: research