Increased Heroin Seeking And Impairment Of Memory After Heroin Self Administration In Ovariectomized Female Rats

Objective Long-term heroin abuse can lead to pituitary-gonadal dysfunction in female and has been accompanied by psychiatric symptoms and cognitive dysfunctions. Furthermore chronic heroin users exhibit high rates of relapse and compulsive drug seeking behavior. However, the impact of heroin exposure on cognitive dysfunction and relapse remains unclear in female. The present studies were to observe whether the ovarian hormones affected heroin self-administration behavior, drug seeking behavior, learning-memory or cognitive functions in female rats and elucidate the relationship between individual vulnerability in cognitive function and heroin reward or relapse.Methods In the present study, adult female rats with or without ovariectomy (VOX) were trained under the fixed-ratio 1 (FR1) schedule for self-administration of heroin at 25g ? kg×25 times i.v., 4 h/day for 14 consecutive days. Reinstatement of heroin seeking were tested followed nose pokers were extinguished in the presence of drug-paired cues or a priming injection of heroin (0.25 mg/kg, s.c.). A variety of behaviors, including fear condition memory, cognitive performance on an object exploration task, and depressive- and anxiety-like behavior before heroin self-administration and after 2 wk of heroin withdrawal were tested.Results Heroin self-administration produced escalation of daily heroin intake in all rats, the initiation and maintenance of heroin intravenous self-administration is not different in the female and VOX rats. During reinstatement testing following exposure to conditioned-cues and drug-priming injection with cues, VOX females produced a significant robust reinstatement behavior than that of normal females. Both of controlled and VOX rats displayed the memory deficits induced by heroin self-administration and anxious, but did not showed the freezing time in forcing-swim behaviors. In addition, the cognitive impairment of female rats correlated closely to heroin self-administration.Conclusion The drug seeking were enhanced in the ovariectomized, suggesting the sexual cycle disorder led by long-term use of heroin can promote further reinstatement behavior. Heroin exposure induces the cognitive deficit which is associated with heroin relapse so novelty-seeking behavior is of particular importance for predicting the susceptibility of female heroin users.