TY - JOUR
T1 - The activity-regulated cytoskeleton-associated protein, Arc/Arg3.1, influences mouse cocaine self-administration
AU - Penrod, Rachel D
AU - Thomsen, Morgane
AU - Taniguchi, Makoto
AU - Guo, Yuhong
AU - Cowan, Christopher W
AU - Smith, Laura N
N1 - Copyright © 2019 Elsevier Inc. All rights reserved.
PY - 2020/1
Y1 - 2020/1
N2 - The 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. However, following normal saline-extinction, wild type (WT) mice show a classic inverted-U dose-response function, while Arc/Arg3.1 knockout (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 contribute to addiction as a regulator of drug-taking vulnerability under different drug availability conditions.
AB - The 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. However, following normal saline-extinction, wild type (WT) mice show a classic inverted-U dose-response function, while Arc/Arg3.1 knockout (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 contribute to addiction as a regulator of drug-taking vulnerability under different drug availability conditions.
U2 - 10.1016/j.pbb.2019.172818
DO - 10.1016/j.pbb.2019.172818
M3 - Journal article
C2 - 31682894
SN - 0091-3057
VL - 188
SP - 172818
JO - Pharmacology Biochemistry and Behavior
JF - Pharmacology Biochemistry and Behavior
ER -