Enhanced functional responsiveness of the dopaminergic system--the mechanism of anti-immobility effects of antidepressants in the behavioural despair test in the rat.
Imipramine, desipramine, maprotiline and atypical antidepressants such as mianserin, trimipramine and levoprotiline were tested in the behavioural despair test in rats. After chronic treatment (twice daily for 7 days), all the drugs, including trimipramine and levoprotiline, significantly reduced the immobility of rats subjected to forced swimming. Of particular interest are the findings with levoprotiline, which in contrast to other antidepressant drugs did not exert any direct or indirect influence on the metabolism of catecholamines and does not seem to interact with the known receptor systems, except the H1 receptors. However, antihistaminics, such as mepyramine and promethazine (5 and 10 mg/kg i.p.) reduced immobility after single doses but were, in contrast to levoprotiline, inactive after chronic treatment. The anti-immobility effect of levoprotiline, as reported for other antidepressants, appears to be related to enhanced dopaminergic function, since it was antagonised by haloperidol and sulpiride, but not by prazosin. The findings of this study therefore support the assumption that dopaminergic activation is critically involved in the anti-immobility effects of antidepressants. Further, the findings support the predictive value of the test since antidepressant properties of levoprotiline have been observed clinically.
Delini-Stula
A
A
Biology Research Laboratories, Pharmaceuticals Division Ciba-Geigy Ltd, Basle, Switzerland.
Radeke
E
E
van Riezen
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D007103:Immobilization; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D011398:Promethazine / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D013469:Sulpiride / Q000494:pharmacology
D000928:Antidepressive Agents; D013469:Sulpiride; D011398:Promethazine; D011738:Pyrilamine; D011224:Prazosin