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Noradrenergic denervation alters serotonin2-mediated behavior but not serotonin2 receptor number in rats: modulatory role of beta adrenergic receptors

AS Eison, FD Yocca and G Gianutsos

Section of Pharmacology and Toxicology, School of Pharmacy, University of Connecticut, Storrs.

Recent behavioral evidence suggests that enhancement of noradrenergic neurotransmission may alter the functional sensitivity of serotonin2 (5- HT2) receptors in the central nervous system. The present studies have examined the effects of two types of noradrenergic denervation [neurotoxic: via N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) treatment; and pharmacologic: via chronic beta adrenergic receptor blockade] on the 5-HT2-mediated head shake response and cortical beta adrenergic and 5-HT2 receptor number in the rat. No changes in quipazine-induced head shakes were observed 3 days after DSP4 lesion. However, the frequency of head shakes was significantly enhanced 10 days after DSP4 treatment in the presence of a 39% up-regulation of beta adrenergic receptors. Pretreatment with propranolol 10 days after DSP4 lesion selectively antagonized the enhancement of the behavioral response to quipazine without altering base-line response rate, whereas pretreatment with the 5-HT2 antagonist ketanserin totally blocked head shakes in both control and DSP4-treated rats. Pharmacologic denervation achieved by continuous (14 day) administration of the beta adrenergic antagonist propranolol also resulted in a potentiation of the head shake response (274% of control) and an upregulation of beta adrenergic receptors (44%). Conversely, continuous treatment with the beta adrenergic agonist clenbuterol resulted in a marked reduction in head shakes (36% of control) with a concomitant 29% down-regulation of beta adrenergic receptors. 5-HT2 receptor binding was not modified by either DSP4 lesion or continuous administration of beta adrenergic agonists or antagonists. These studies demonstrate that changes in cortical beta adrenergic receptor density may modify 5-HT2-mediated behavior in a manner that is independent of changes in 5-HT2 receptor number.

Volume 246, Issue 2, pp. 571-577, 08/01/1988
Copyright © 1988 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1988 by the American Society for Pharmacology and Experimental Therapeutics.