Anxiety increases the place conditioning induced by cocaine in rats

Some clinical studies have shown that anxiety disorders are often associated with drug dependence, although it remains unclear whether these disorders are primary or secondary to drug abuse. We have investigated whether anxiety may be a factor that predisposes to cocaine use. From an outbred Wistar strain, we have selected male rats regarded as anxious or non-anxious on the basis of their scores on two behavioural tests of unconditioned anxiety, the elevated plus-maze and the light/dark box test. They were also screened for their locomotor activity in an inescapable novel environment and for their preference for novelty presented in a free-choice. Rewarding effects of cocaine (2.5-20 mg/kg; i.p.) were then determined in the conditioned place preference paradigm (CPP). Anxious and non-anxious rats showed no difference in their responsiveness to inescapable novelty or their preference for novelty in a free-choice procedure. Only anxious rats developed a CPP induced by increasing doses of cocaine, the magnitude of CPP induced by the 10 mg/kg dose of cocaine being significantly higher than that observed in anxious rats conditioned with saline. These results suggest that anxiety affects the sensitivity to aversive/anxiogenic effects of cocaine. Thus, anxious rats which were highly responsive to positive effects of cocaine may be more prone to develop cocaine addiction than non-anxious rats.