Interaction between behavioral despair and addictive behaviors in rats

It has been suggested that depression can be either a cause or a consequence of drug abuse, providing a possible explanation for the fact that the prevalence of depression is almost 3-fold higher in drug abusers than in the general population. However, the interaction between depression and drug abuse has not been fully elucidated. To examine the interaction between behavioral despair and addictive behaviors, we used the Porsolt's forced swim test (FST) as a model of behavioral despair, and we used morphine conditioned place preference (CPP) and repeated morphine exposure as models of addictive behaviors. We found that rats exposed to a standard FST (15 min on day 0 training) rather than a weak FST (10 min on day 0 training) exhibited behavioral despair, which selectively potentiated morphine CPP (mCPP) but not food CPP (fCPP). The antidepressant imipramine (15 mg/kg, i.p.), which blocked the behavioral despair, prevented the standard FST potentiated morphine CPP. Conversely, repeated exposure to morphine (10 mg/kg, s.c.) for 6, 12 or 20 days decreased, had no effect on, or increased the immobility time, respectively, in the subsequent standard FST. Furthermore, repeated morphine exposure for 20 days exacerbated the pre-existing behavioral despair. Thus, our findings suggest that behavioral despair may increase the vulnerability of individuals to opiate abuse, which may in turn enhance behavioral despair.

Research Highlights
► Depression-like behaviors enhance addiction-like behaviors.
► Antidepressant blocks both depression- and addiction-like behaviors.
► Morphine exposure affects depression-like behavior differentially.
► Long term morphine exposure exacerbates pre-existing behavioral despair.