Reversal of Antidepressant Action by Dopamine Antagonists in an Animal Model of Depression

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 1991 Jan 1

PMID 1838201

Citations 25

Authors

D Sampson

P Willner

R Muscat

Affiliations

Soon will be listed here.

Abstract

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.

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