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Reversal of antidepressant action by dopamine antagonists in an animal model of depression

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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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  1. Psychology Department, City of London Polytechnic, Old Castle Street, E1 7NT, London, UK

    David Sampson, Paul Willner & Richard Muscat

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  1. David Sampson
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  2. Paul Willner
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  3. Richard Muscat
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Sampson, D., Willner, P. & Muscat, R. Reversal of antidepressant action by dopamine antagonists in an animal model of depression. Psychopharmacology 104, 491–495 (1991). https://doi.org/10.1007/BF02245655

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  • DOI: https://doi.org/10.1007/BF02245655

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