Sex differences in the acquisition and maintenance of cocaine and nicotine self-administration in rats

Abstract

Rationale Consistent sex differences are observed in human drug addiction, with females often exceeding males on drug intake. However, there is still a need for animal models for some aspects of addiction such as acquisition of drug self-administration and the subsequent development of drug-seeking. Objectives The present study examined sex differences in the acquisition of self-administration of two widely used stimulants, cocaine and nicotine. Methods Male and female rats self-administered cocaine (0.4 mg/kg/infusion) or nicotine (0.03 mg/kg/infusion) daily under a fixed-ratio 1 (FR 1) schedule until acquisition criteria were met (maximum of 30 sessions). The self-administration criterion for cocaine was ≥20 infusions in a 2 h session and ≥5 infusions in a 1 h session for nicotine. Sex differences were assessed by examining the percentage of rats that met acquisition criteria, the number of sessions to meet criteria and the number of infusions earned during the maintenance phase. Results A significantly higher percentage of male rats acquired both cocaine and nicotine self-administration than females, and males met acquisition criteria in fewer sessions. However, after criteria were met, females self-administered more cocaine than males during the first 5 days of maintenance. There were no sex differences in nicotine infusions post acquisition. Conclusions Differences in acquisition amongst sexes can reveal factors that are integral to initiation of drug use, an often overlooked phase of drug addiction.

Sex differences in attenuation of nicotine reinstatement after individual and combined treatments of progesterone and varenicline

“…The present results showing that adult female and male rats took similar numbers of infusions during NIC self-administration, which is consistent with a number of previous reports [8,43,52,39,53,54]. While enhanced motivation and NIC intake in female rats has been reported in some studies [52,55,56], this typically occured only when increased behavioral output was required.…”

“…The age of the rats was between 63–77 days upon arrival from Harlan Sprague-Dawley Inc. (Madison, WI), with females and males matched for age. Acquisition and maintenance data from a subset of rats (approximately half of the males and females) were analyzed for acquisition differences and published as part of a separate study [43]. Upon arrival, all rats were pair-housed in plastic cages and habituated to the laboratory for at least 3 days with ad libitum access to food (Teklad 2018, Harlan Laboratories, Madison, WI) and water prior to beginning experiments.…”

Sex differences in reinstatement of cocaine-seeking with combination treatments of progesterone and atomoxetine

“…Data from the first 5 sessions of maintenance for some animals were previously presented in Swalve et al (2015). There was a significant main effect of sex on total infusions [ F (1, 87)=6.772, p < 0.01] and a main effect of session [ F (9, 783)=3.301, p < 0.001], but there was no interaction.…”

“…The vertical bar with an asterisk indicates a difference between males (n=43) and females (n=45) on total infusions during the 10 sessions of maintenance. Data from some animals on the first 5 sessions of maintenance has been previously published (Swalve et al, 2015) * = p < 0.05.…”

Cocaine self-administration and reinstatement in female rats selectively bred for high and low voluntary running

“…At the end of 10 sessions, approximately 85% of the LVRs had acquired cocaine self-administration (Figure 1A). In comparison, cocaine studies from our lab that employ female Wistar rats typically report that 20–55% acquire cocaine self-administration following 10 training sessions (e.g., Carroll et al, 2002; Perry et al, 2005, 2008; Swalve et al, 2015); Larson and Carroll (2005) did not report the percentage of HiR and LoR rats that acquired. Thus in comparison to other studies, LVR rats appear more vulnerable to developing cocaine-seeking behaviors than HVR rats, which appear to be more like the typical (i.e., wild-type) out-bred Wistar rats.…”