Activation of G protein-coupled estradiol receptor 1 in the dorsolateral striatum enhances motivation for cocaine and drug-induced reinstatement in female but not male rats

Biology of Sex Differences

Molly K. Logsdon¹  Brianna C. Graham²  Kendra G. Beaudoin²  Jacqueline A. Quigley³  Jill B. Becker³ 

[1] Michigan Neuroscience Institute, University of Michigan, 48109, Ann Arbor, MI, USA;Psychology Department, University of Michigan, 48109, Ann Arbor, MI, USA;Psychology Department, University of Michigan, 48109, Ann Arbor, MI, USA;Michigan Neuroscience Institute, University of Michigan, 48109, Ann Arbor, MI, USA;

关键词: GPER1;    Dorsolateral striatum;    Sex differences;    Motivation;    Addiction;    Cocaine;   

DOI  :  10.1186/s13293-021-00389-w

来源: Springer

【 摘 要 】

BackgroundEstradiol potentiates drug-taking behaviors, including motivation to self-administer cocaine and reinstatement of drug-seeking after extinction in females, but not males. The dorsolateral stratum (DLS) is a region of the brain implicated in mediating drug-seeking behaviors and, more specifically, is a target brain area to study how estradiol regulates these behaviors. The estradiol receptors α, β, and G protein-coupled estradiol receptor 1 (GPER1) are all present in the DLS. In this study, the effects of activating GPER1 in the DLS on drug-seeking are investigated.MethodsGonad-intact male and female rats were trained to self-administer cocaine (0.4 mg/kg/inf) on a fixed-ratio 1 schedule of reinforcement. For 4 weeks, animals underwent testing on a progressive ratio schedule of reinforcement to determine their motivation to attain cocaine. Halfway through progressive ratio testing, a selective agonist targeting GPER1 (G1) was administered intra-DLS to determine the contribution of GPER1 activation on motivation for cocaine. The effects of intra-DLS GPER1 activation on drug-induced reinstatement after extinction were subsequently determined.ResultsActivation of GPER1, via intra-DLS G1 administration, potentiated females’ motivation to self-administer cocaine. There was no effect of prior G1 treatment on extinction of cocaine-taking in females; however, G1 treatment resulted in greater drug-induced reinstatement (10 mg/kg cocaine, i.p.). There were no effects of intra-DLS GPER1 activation observed on motivation for cocaine or cocaine-induced reinstatement of responding in males.ConclusionsThese results support the conclusion that activation of GPER1 in the DLS enhances cocaine-seeking behaviors for female, but not male rats.

【 授权许可】

CC BY