Prior access to a sweet is more protective against cocaine self-administration in female rats than in male rats

Abstract

It is well established that female rats are more sensitive than male rats to the reinforcing effects of cocaine (Lynch, 2008 for review). We hypothesized that greater preference for cocaine would support greater avoidance of a cocaine-paired taste cue in female vs. male rats. Moreover, at least in male rats, greater avoidance of the taste cue is associated with greater cocaine self-administration (Grigson & Twining, 2002). Thus, we anticipated that female rats would not only demonstrate greater avoidance of the drug-paired taste cue, but greater drug-taking as well. We tested these hypotheses by examining avoidance of a saccharin cue in male and female rats following several pairings with self-administered saline or cocaine (0.16, 0.33, or 0.66 mg/infusion). Contrary to expectations, the results showed that female rats exhibited less avoidance of the cocaine-associated saccharin cue than male rats and self-administered less, rather than more, cocaine, Thus, while female rats reportedly take more drug than male rats when the drug is presented in the absence of an alternative reward, they take less drug than male rats when the opportunity to self-administer cocaine is preceded by access to a palatable sweet. Females, then, may not simply be more sensitive to the rewarding properties of drug, but also to the reinforcing properties of natural rewards and this increase in sensitivity to sweets may serve to protect against drug-taking behavior.

Sweet taste liking is associated with subjective response to amphetamine in women but not men

“…On the other hand, it is possible that sensitivity to sweet rewards could be a protective factor against drug abuse in females. A recent animal study tested this possibility by assessing consumption of a saccharine cue that signaled subsequent access to cocaine (Cason and Grigson 2013). The authors found that females consumed more of the saccharine cue and less subsequent cocaine, whereas males avoided the saccharin cue and consumed greater amounts of cocaine.…”

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

“…Behavioral factors such as dose of drug, length of access, and even pair-housing (Westenbroek et al 2013) or prior access to sweets (Cason and Grigson 2013) may be integral to the development of sex differences in cocaine acquisition. A biological basis for cocaine acquisition has been suggested by Hu and colleagues (2004).…”

Once is too much: Conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats.

“…Finally, we have identified a number of factors that affect avoidance of a drug-paired cue and/or responding for drug. For example, female Sprague-Dawley rats exhibit more acceptance of a cocaine-paired saccharin cue and less cocaine self-administration in the taste-drug model than male rats (Cason & Grigson, 2013). Environmental enrichment during adulthood reduces acquisition of cocaine self-administration in male rats (Puhl et al, 2012).…”