A comparison of the behavioral effects of minaprine, amphetamine and stress

Different types of clinically effective antidepressants prevent the behavioral effects of experimental stress, and some of these treatments affect mesolimbic dopamine (DA) functioning. Animal studies have demonstrated that repeated psychostimulant administration and repeated or chronic stressful experiences also affect mesolimbic DA functioning. These results could suggest homologies among stress, psychostimulants and antidepressants. The present experiments show that either repeated stress (120 min restraint daily for 10 consecutive days) or subchronic treatment with the antidepressant minaprine (5 mg/kg daily for 10 consecutive days) significantly reduced the inhibitory effect of 120 min of restraint on climbing, a behavioral response dependent on mesolimbic DA functioning. However, the antidepressant did not induce the altered sensitivity of presynaptic DA receptors promoted by repeated stress. Chronic stressful experience (13 days of food restriction) and repeated amphetamine (2.5 mg/kg daily for 10 consecutive days) were as effective as subchronic minaprine in reducing immobility in the Porsolt's swimming test. However, whilst both stress and amphetamine enhanced struggling, minaprine promoted swimming. Finally, chronically stressed mice and mice pretreated with amphetamine showed enhanced sensitivity to amphetamine-induced locomotion, whilst this effect was absent in animals pretreated with the antidepressant. These results indicate that although chronic and repeated stress as well as amphetamine have some antidepressant-like behavioral effects, their mode of action could be different from that of clinically active substances.