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 locomotion were studied in separate experiments. Nifedipine, a drug which interacts selectively with dihydropyridine (DHP) binding sites, reduced immobility time in the mouse forced swimming test and tail suspension test, but lacked activity in the differential-reinforcement-of-low-rate schedule in rats (DRL 72 s). The effects of nifedipine in the tail suspension test was partly antagonized by Bay K 8644, a DHP channel activator, indicating that its effect involved L-type calcium channel. Several other DHP drugs (nicardipine, nitrendipine, isradipine, felodipine and nimodipine) also showed antidepressant-like properties in the tail suspension test, whereas amlodipine, a less selective compound, lacked activity. In contrast to the DHP drugs, verapamil and (-)emopamil (which act at the phenylalkylamine binding sites), diltiazem and clentiazem (benzothiazepine binding sites), and the non-selective drug, flunarizine, were inactive in the tail suspension test. Negative results were also obtained with verapamil, diltiazem and flunarizine in the forced swimming test and with flunarizine on DRL 72 s responding. The present results show that DHP channel blockers displayed 'antidepressant-like' properties in mice. There was little dissociation, however, between the doses that produced antidepressant effects and those that decreased locomotor activity.
Cohen
C
C
CNS Research Department, Synthélabo Recherche, Bagneux, France.
Perrault
G
G
Sanger
D J
DJ
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D020746:Calcium Channels, L-Type; D003216:Conditioning, Operant / Q000187:drug effects; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D013550:Swimming / Q000523:psychology
D000928:Antidepressive Agents; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D009419:Nerve Tissue Proteins; D009543:Nifedipine