Involvement of angiotensin-converting enzyme inhibition in reversal of helpless behavior evoked by perindopril in rats.
Several clinical investigations have suggested that captopril, an angiotensin-converting enzyme inhibitor (ACEI) currently used as an anti-hypertensive agent, exhibits antidepressant properties in humans. In the present study we evaluated the action of perindopril, another ACEI, and two of its metabolites, the di-acide form perindoprilat, which possesses ACE inhibitory properties, and BDM-4, an inactive metabolite, in the learned helplessness paradigm. In order to confirm a possible action of these drugs via dipeptidyl carboxypeptidase inhibition, we also investigated two inactive analogues of perindopril and perindoprilat. Perindopril (0.06-8 mg/kg per day) and perindoprilat (0.25-8 mg/kg per day) induced a reversal of escape deficits. BMD-4 and two analogues failed to reverse helpless behavior. These results support the hypothesis that ACE inhibition is a key factor in the behavioral antidepressant-like activity of perindopril and perindoprilat.
Martin
P
P
Département de Pharmacologie, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Massol
J
J
Scalbert
E
E
Puech
A J
AJ
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002268:Carboxypeptidases / Q000037:antagonists & inhibitors; D004597:Electroshock; D006380:Helplessness, Learned; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D020913:Perindopril; D051381:Rats; D011919:Rats, Inbred Strains
D000806:Angiotensin-Converting Enzyme Inhibitors; D007211:Indoles; C053500:perindoprilat; D002268:Carboxypeptidases; D007703:Peptidyl-Dipeptidase A; D020913:Perindopril