Acute stress worsens the deficits in appetitive behaviors for social and sexual stimuli displayed by rats after long-term withdrawal from morphine.

RATIONALE: Negative affective states, e.g., anhedonia, are suggested to be involved in the long-lasting motivational processes associated with relapse. Here, we investigated whether anhedonic behaviors could be elicited by an acute stress after protracted abstinence from morphine. OBJECTIVES: The behavioral responses to natural stimuli following exposure to an acute stress were examined after 14 days of withdrawal from morphine. Male rats were pretreated with either a binge-like morphine regimen or daily saline injections for 5 days. The motivation for two natural stimuli, i.e., a social stimulus (male rat) and a sexual stimulus (estrous female rat), was measured, following exposure to an acute stress (intermittent foot shock, 0.5 mA * 0.5 s * 10 min; mean inter-shock interval 40 s), under three conditions: free approach and effort- and conflict-based approaches. RESULTS: Foot-shock-induced stress did not influence free-approach behavior (sniffing time) towards the social or sexual stimulus. However, in the effort-based approach task, the stressed morphine-withdrawn rats demonstrated an attenuated motivation to climb over a partition to approach the social stimulus while the stressed saline-pretreated rats showed an increased motivation to approach the social stimulus. When an aversive stimulus (pins) was introduced in order to induce an approach-avoidance conflict, both drug-withdrawn and drug-naïve groups exhibited a bimodal distribution of approach behavior towards the sexual stimulus after the stress was introduced, i.e., the majority of rats had low risky appetitive behaviors but a minority of them showed rather highly "risky" approach behavior. CONCLUSIONS: The acute stress induces differential motivational deficits for social and sexual rewards in protracted drug-abstinent rats.This work was supported by the National Foundation of Natural Science (grant: 31000463) to YJ Bai. D Belin is supported by the Wellcome Trust (grant: 109738/Z/15/Z), the Leverhulme Trust (grant: RPG-2016-117), and the Medical Research Council (MR/N02530X/1). XG Zheng is supported by the Knowledge Innovation Program of Chinese Academy of Sciences (grant: KJZD-EWL04-2)