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

Psychopharmacology (Berl). 2017 Jun;234(11):1693-1702. doi: 10.1007/s00213-017-4571-3. Epub 2017 Mar 9.


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 However, in the effort-based approach task, the stressed morphine-withdrawn rats demonstrated an attenuated motivation to climb over a partition to approach the social stimulus while the stressed saline-pretreated rats showed an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 When an aversive stimulus (pins) was introduced in order to induce an approach-avoidance conflict, both drug-withdrawn and drug-naïve groups exhibited a bimodal distribution of approach behavior towards the sexual stimulus after the stress was introduced, i.e., the majority of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.

Keywords: Anhedonia; Appetitive behavior; Protracted morphine withdrawal; Sexual reward; Social reward; Stress.

MeSH terms

  • Animals
  • Appetitive Behavior / drug effects
  • Appetitive Behavior / physiology*
  • Dose-Response Relationship, Drug
  • Female
  • Interpersonal Relations*
  • Male
  • Morphine / administration & dosage*
  • Morphine Dependence / psychology
  • Rats
  • Sexual Behavior, Animal / drug effects
  • Sexual Behavior, Animal / physiology*
  • Stress, Psychological / psychology*
  • Substance Withdrawal Syndrome / psychology*
  • Time Factors


  • Morphine