Placebo affects the performance of rats in models of depression: is it a good control for behavioral experiments?

Experimental design of behavioral studies in animals generally includes pla cebo-treated controls. However, when placebo is administered by injection i n experimental models of psychiatric diseases such as depression, where str ess may affect the execution of the behavioral test, it is possible that in jection per se may influence the behavioral response. Rats injected with cl omipramine hydrochloride (1, 10 or 50 mg/kg), as compared to animals inject ed with physiological saline as placebo, showed a dose-dependent decrease o f the immobility time in the despair test and of the number of floor units explored in the open field in the reserpine test. However, when animals inj ected with placebo or clomipramine 50 mg/kg were compared with untreated in tact controls, it was found that the immobility time in the despair test wa s higher in the placebo-treated animals than in untreated intact controls. A difference was found between clomipramine-injected animals and untreated intact controls. In contrast, rats tested in the reserpine test. which is b ased on repeated drug injections, no difference was found between placebo-t reated animals and untreated intact controls. These results indicate that s tressful procedure of the experimental design may change the response of an imals in behavioral tests. Studies with experimental models of depression, where stressful procedures are used, should include a control group of untr eated intact animals. (C) 2001 Elsevier Science B.V./ECNP. All rights reser ved.