Abstract

Substance use disorders involve a cyclical pattern of escalating drug use, abstinence from the drug of choice, and subsequent relapse. Relapse can be driven by stressful life events causing drug cravings and preoccupation, leading to the return of escalating drug use. Different models have been proposed to study this phenomenon in animals. Often users abstain due to the negative consequences of drug-seeking and taking. As such, voluntary abstinence models were created whereby animals often choose to abstain of their own volition. One of the ways to induce this is through a punishment-imposed abstinence model, where abstinence is achieved through punishing animals’ drug-seeking or drug-taking behaviours. Past research in our laboratory using this model has shown that acute food deprivation stress increases heroin-seeking following abstinence. However, there is little research on the generalization of the effects of acute food deprivation stress on heroin-seeking to other acute stressors using a punishment model. Individual differences in many traits correlate with drug use behaviours. Specifically, traits like reward-seeking, anxiety-like behaviour, and novelty-seeking have been associated with different aspects of drug use. Greater levels of reward-seeking, anxiety-like, and novelty-seeking behaviours are thought to increase the risk of substance use. Finally, sex differences are well documented in addiction research due to biological and sociological reasons. Animal models further support sex differences: females often escalate to drug use faster, have higher intake levels, and relapse more. Furthermore, females are more resistant to punishment than their male counterparts, which may mean that females are more resistant to punishment-imposed abstinence. The current study had three aims: (1) to investigate the generalization of the effect of acute food deprivation to other acute stressors in a punishment-imposed abstinence model: restraint stress, forced swim stress, and foot-shock stress; (2) to measure the degree to which individual differences predict stress-induced relapse using the following tests: sucrose preference (SP) test, elevated plus maze (EPM), open field test (OF), and tail-flick (TF) test; and (3) assess differences between male and female rats in punishment-imposed abstinence and stress-induced drug-relapse behaviour. Adolescent male and female Long-Evans rats underwent SP, EPM, OF, and TF testing. Subsequently, rats were trained to self-administer heroin (0.1 mg/kg/infusion) under a seek-take chain for at least 14 days. Rats then underwent punishment-imposed abstinence for 8 days. Afterwards, rats were exposed to a stress condition (males: food deprivation, restraint, forced swim, or footshock; females: restraint, forced swim, or food deprivation) before undergoing a heroin-seeking test. It was found that the effect of acute food deprivation stress on relapse generalized only to forced swim-induced relapse in both male and female rats. Individual differences in traits of anxiety, novelty-seeking and reward-seeking did not reliably predict drug relapse. Male and female rats did not differ in punishment-imposed abstinence or stress-induced relapse behaviour.