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Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation

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Summary

Chronic (14 day) administration of several pharmacologically-distinct antidepressant drugs resulted in marked reductions in the serotonin2 (5-HT2)-mediated quipazine-induced head shake response which were accompanied by significant reductions in the density of cortical Β-adrenergic and 5-HT2 binding sites. Noradrenergic (DSP4[N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine]-induced) and serotonergic (5,7-DHT[5,7-dihydroxytryptamine]-induced) lesions either attenuated or blocked antidepressant-induced reductions in 5-HT2-mediated behavior. DSP4- and 5,7-DHT lesions did not alter the down-regulation of 5-HT2 binding sites produced by imipramine, desipramine, phenelzine or iprindole. To a large extent, the antagonism of antidepressant-induced reductions in 5-HT2-mediated behavior was coincident with the blockade of down-regulation of Β-adrenergic binding sites by both noradrenergic and serotonergic denervation. The functional interrelationship of 5-HT2 and Β-adrenergic receptors suggested by the present findings may provide insight into a common mechanism underlying the action of pharmacologically-distinct antidepressant drugs.

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Eison, A.S., Yocca, F.D. & Gianutsos, G. Effect of chronic administration of antidepressant drugs on 5-HT2-mediated behavior in the rat following noradrenergic or serotonergic denervation. J. Neural Transmission 84, 19–32 (1991). https://doi.org/10.1007/BF01249106

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