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. 1983 Jan;78(1):89–96. doi: 10.1111/j.1476-5381.1983.tb09367.x

The effect of chronic antidepressant administration on β-adrenoceptor function of the rat pineal

PJ Cowen, Sheila Fraser, DG Grahame-Smith, AR Green, Clare Stanford
PMCID: PMC2044787  PMID: 6130811

Abstract

1 The β-adrenoceptor agonist, isoprenaline (1.5-3.0 mg kg-1 intravenously), produced a dose-related increase in rat pineal melatonin content. This increase was prevented by pretreatment with the selective β1-adrenoceptor antagonist, atenolol (2 mg kg-1), but not by the β2-adrenoceptor antagonist, butoxamine (2 mg kg-1). The β2-adrenoceptor agonist, terbutaline (5.0 mg kg-1), produced a moderate increase in pineal melatonin content.

2 Repeated daily administration of desmethylimipramine (10 mg kg-1 for 10 days) and maprotiline (10 mg kg-1 for 10 days), antidepressants predominantly inhibiting noradrenaline (NA) uptake, reduced the isoprenaline-induced increase in pineal melatonin content. Amitriptyline (20 mg kg-1 for 14 days), a drug which inhibits both NA and 5-hydroxytryptamine (5-HT) uptake, had a similar effect. The β-adrenoceptor agonist, clenbuterol (5 mg kg-1 for 14 days), also attenuated the increase in pineal melatonin produced by isoprenaline.

3 In contrast, chronic administration of the selective 5-HT uptake inhibitor, fluoxetine (10 mg kg-1 for 10 days), or the antidepressants, iprindole and mianserin (both 20 mg kg-1 for 14 days), which do not inhibit monoamine uptake, failed to reduce the increase in pineal melatonin following isoprenaline. Repeated electroconvulsive shock was similarly without effect.

4 Ten hours after the final dose of desmethylimipramine (10 mg kg-1) once daily for 10 days there was no change in the usual dark phase increase in pineal melatonin.

5 The data suggest that repeated administration of certain antidepressant drugs results in reduced pineal β-adrenoceptor sensitivity. However the lack of change in the dark phase increase in pineal melatonin following repeated desmethylimipramine, implies that the reduced ß-adrenoceptor sensitivity may be part of an adaptive process which maintains normal pineal function. Therefore the decrease in β-adrenoceptor number in the brain reported after chronic antidepressant administration may not be associated with a change in overall synaptic function.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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