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We studied 13 known or potential antidepressants, choosen in different pharmacological classes: desipramine, imipramine, nialamide, dexamphetamine, AHR 1118, amineptine, iprindole, mianserine, nomifensine, salbutamol, TRH viloxazine, zimelidine. Each of these compounds was studied on 8 psychopharmacological tests: motor activity, reserpine induced hypothermia, reserpine induced ptosis, oxotremorine induced hypothermia, oxotremorine induced tremors, high doses apomorphine induced hypothermia, potentiation of toxic effects of yohimbine, behavioural despair. Clinical active compounds are efficient on yohimbine test and at least on one model of hypothermia; with a few exceptions, easy to explain, substances with a clearly demonstrated antidepressant activity in human have some common effects; these common effects can be used to predict, from animal experiments, an antidepressant effect in man.

Common effects of four beta-adrenergic blocking drugs have been investigated in mice using classical and new psychopharmacological tests. Propranolol, alprenolol, practolol and penbutolol reduced the increase in locomotor activity produced by reserpine after MAO inhibition; they produce hypothermia when associated with amphetamine and they increase oxotremorine-induced hypothermia. Regarding these three tests the studied substances ranged themseleves in the same order of potency: penbutolol greater than propranolol greater than alprenolol greater than practolol. Propranolol and penbutolol decreased the toxicity provoked in crowded mice by amphetamine or by the association pargyline-reserpine; alprenolol and practolol did not. Propranolol, penbutolol and alprenolol antagonized the amphetamine-induced increase in motor activity; practolol did not. When used at doses for which d-l propranolol was active, the dextrogyre isomer of propranolol was without effect whatever the test studied. It is suggested that for the selection of a beta-blocking drug, regarding central effects in man, the tests described would deserve consideration.

The concept of inhibition in psychopharmacology is discussed by presenting different models of behavioral inhibition in animals. The inhibitions induced by fear or anxiety appear as a result of punishment introduction into an unknown situation, frustration... These inhibitions are particularly sensitive to minor tranquilizers. The inhibitions induced by "fatigue" appear when avoidance situations continue for 24 hours or when a situation demands a marked increase of animal activity to obtain the same reward (food). These inhibitions are particularly sensitive to psychoanaleptics. The inhibition induced by placing a animal in an inescapable situation is particularly sensitive to antidepressants.

Some of the substances studied modified the effects of the two barbiturates as expected and in the same direction: --chlorpromazine and diazepam increased the effects; --amphetamine and caffeine decreased them. Barbital, unlike pentobarbital, undergoes almost no metabolic transformation. This explains why pentobarbital is potentiated in the presence of proadifen, an inhibitor of liver microsomial enzymes, whereas the effect of barbital is unchanged, and probably explains similar results obtained with iproniazide and imipramine. For the same reason, rifampicine, an enzyme inducer, antagonizes the effect of pentobarbital without affecting that of barbital. The dissociated effects obtained with other substances are more difficult to explain: --increased effects of barbital without modification of the effects of pentobarbital (sulpiride); --decreased effects of barbital without modification of the effects of pentobarbital (methylphenidate, nomifensine, amineptine, oxolinic acid, methysergide); --decreased effects of barbital with increased effects of pentobarbital (viloxazine). Two hypotheses may be considered: 1. The study of barbital and pentobarbital concentrations in blood and brain would allow to exclude a pharmacokinetic interaction; 2. Barbital does not act through the same mechanism as pentobarbital.

Four effects of nomifensine were studied in interaction with a dopamine receptor blocker (pimozide) and a beta-adrenergic receptor blocker (propranolol). The effects of nomifensine were divided into two categories: 1. Psychomotor stimulant effect a) Stimulation of locomotor activity in mice b) Stereotyped behavior in rats 2. Antidepressant effect a) Antagonism of hypothermia caused by reserpine in mice b) Potentiation of yohimbine-induced toxicity in mice. The psychomotor stimulant effects were antagonized by pimozide but not by propranolol. The antidepressant effects were antagonized by propranolol but not by pimozide. Our results support the hypothesis that nomifensine acts via both dopaminergic and noradrenergic mechanisms subserving distinct behavioral effects, psychomotor stimulant and antidepressant, respectively.