Heroin self‐administered female rats display impaired memory and increased heroin‐seeking behavior

Abstract

Heroin dependence is frequently accompanied with cognitive dysfunction and psychiatric symptoms, but the impact of heroin self‐administration on these remains elucidated. Adult female rats with or without ovariectomy (VOX) were trained under the fixed‐ratio 1 (FR1) schedule for self‐administration of heroin (0.05 mg/infusion, i.v., 4 h/d×14 d). Nose pokers were extinguished prior to reinstatement testing, which consisted of presentation of drug‐paired cues or a priming injection of heroin (0.25 mg/kg, s.c.). After 2 wk of heroin withdrawal, rats were examined in a variety of behavioral tests, including object recognition and fear condition. All the rats produced escalation of daily heroin intake. During reinstatement testing following exposure to conditionedcues and drug‐priming injection with cues, VOX females produced a robust reinstatement behavior. Compared to normal females, VOX rats displayed more susceptibility to memory deficits after heroin self‐administration. These results suggest that ovarian hormones deficit may enhance drug‐primed reinstatement and facilitate cognitive deficits and other psychiatric disorders, such as anxiety and depression, after chronic heroin exposure in female rats.