Dopaminergic mechanism of imipramine action in an animal model of depression.
Rats, subjected chronically (10-12 weeks) to a variety of mild, unpredictable stressors, showed a decrease in their consumption of weak sucrose solutions; normal behavior was restored by chronic (5-9 weeks) treatment with the tricyclic antidepressant imipramine. Acute administration of the dopamine receptor antagonist pimozide or the specific dopamine D2 receptor antagonist raclopride had no effect in nonstressed animals and in vehicle-treated stressed animals, but both drugs selectively reversed the improvement of performance in imipramine-treated stressed animals. The 5HT antagonist metergoline increased sucrose consumption in all groups. The data suggest that the mechanism of action of imipramine in this model is an increase in functional activity at dopamine (DA) synapses.
Muscat
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Psychology Department, City of London Polytechnic, England.
Sampson
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D
Willner
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P
D000818:Animals; D001070:Appetitive Behavior / Q000187:drug effects; D001143:Arousal / Q000187:drug effects*; D003866:Depressive Disorder / Q000188:drug therapy*; D004326:Drinking / Q000187:drug effects; D007099:Imipramine / Q000008:administration & dosage*; D008297:Male; D008711:Metergoline / Q000494:pharmacology; D010868:Pimozide / Q000494:pharmacology; D020891:Raclopride; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D013649:Taste / Q000187:drug effects
D011954:Receptors, Dopamine; D012457:Salicylamides; D008711:Metergoline; D010868:Pimozide; D020891:Raclopride; D007099:Imipramine