ASSESSMENT OF THE ANTIDEPRESSANT-LIKE EFFECTS OF L-TYPE VOLTAGE-DEPENDENT CHANNEL MODULATORS

L-type voltage-dependent calcium channel blockers acting at different sites were tested in animal models of depression. Their effects on loc omotion were studied in separate experiments. Nifedipine, a drug which interacts selectively with dihydropyridine (DHP) binding sites, reduc ed immobility time in the mouse forced swimming test and tail suspensi on test, but lacked activity in the differential-reinforcement-of-low- rate schedule in rats (DRL 72 s). The effect of nifedipine in the tail suspension test was partly antagonized by Bay K 8644, a DHP channel a ctivator, indicating that its effect involved L-type calcium channels. Several other DHP drugs (nicardipine, nitrendipine, isradipine, felod ipine and nimodipine) also showed antidepressant-like properties in th e tail suspension test, whereas amlodipine, a less selective compound, lacked activity. In contrast to the DHP drugs, verapamil and (-)emopa mil (which act at the phenylalkylamine binding sites), diltiazem and c lentiazem (benzothiazepine binding sites), and the non-selective drug, flunarizine, were inactive in the tail suspension test. Negative resu lts were also obtained with verapamil, diltiazem and flunarizine in th e forced swimming test and with flunarizine on DRL 72 s responding. Th e present results show that DHP channel blockers displayed 'antidepres sant-like' properties in mice. There was little dissociation, however, between the doses that produced antidepressant effects and those that decreased locomotor activity.