Reversal of antidepressant action by dopamine antagonists in an animal model of depression.
Rats subjected chronically (12 weeks) to a variety of mild, unpredictable stressors showed a reduced consumption of sucrose or a sucrose/saccharin mixture in two-bottle consumption tests (sweet solution versus water). The deficit was apparent within 2 weeks of stress; normal behaviour was restored by chronic (7 weeks) treatment with the tricyclic antidepressants desmethylimipramine (DMI) or amitriptyline (AMI). Acute administration of the dopamine D1 receptor antagonist SCH-23390 1 week after withdrawal, or the dopamine D2 receptor antagonist sulpiride 2 weeks after withdrawal, were without effect in vehicle-treated stressed animals, and in non-stressed animals. However, the DA antagonists selectively reversed the improvement of performance in DMI- or AMI-treated stressed animals. This suggests that an increase in functional activity at DA synapses is the mechanism of action of DMI and AMI in this model.
Sampson
D
D
Psychology Department, City of London Polytechnic, UK.
Willner
P
P
Muscat
R
R
D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000037:antagonists & inhibitors*; D001552:Benzazepines / Q000494:pharmacology; D003866:Depressive Disorder / Q000503:physiopathology*; D004195:Disease Models, Animal; D018492:Dopamine Antagonists; D004327:Drinking Behavior / Q000187:drug effects; D008297:Male; D051381:Rats; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013315:Stress, Psychological / Q000523:psychology; D013395:Sucrose / Q000494:pharmacology; D013469:Sulpiride / Q000494:pharmacology
D000929:Antidepressive Agents, Tricyclic; D001552:Benzazepines; D018492:Dopamine Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D013395:Sucrose; D013469:Sulpiride