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Effects of antidepressant drugs and electroconvulsive shock on pre- and postsynaptic α2-adrenoceptor function in the brain: rapid down-regulation by sibutramine hydrochloride

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Abstract

Clonidine (0.1 mg/kg IP)-induced hypoactivity and mydriasis responses were respectively used as functional indices of pre- and postsynaptic α2-adrenoceptors in mouse brain. A single injection of various antidepressant drugs had no effect on either response when measured 24 h later. However, 14 days' treatment with sibutramine HCl (3 mg/kg IP), dothiepin (50 mg/kg IP), amitriptyline (10 mg/kg IP), desipramine (10 mg/kg IP) or tranylcypromine (10 mg/kg IP) markedly attenuated both clonidine-induced hypoactivity and mydriasis. Repeated administration of zimeldine (10 mg/kg IP), mianserin (10 mg/kg IP) or clenbuterol (5 mg/kg IP) had no effect on either response. Subchronic treatment with sibutramine HCl (3 mg/kg IP; 3 days) also attenuated pre- and postsynaptic α2-adrenoceptor function. Five ECS (200 V, 2 s) spread over 10 days, but not a single shock, reduced the hypoactivity and mydriasis responses to clonidine. Together, the results indicate that pre- and postsynaptic α2-adrenoceptor function is attenuated by repeated treatment with those antidepressants which acutely increase synaptic levels of noradrenaline. These adrenergic receptor populations are also desensitized by ECS, although this effect is probably mediated via a different mechanism. Finally, the rapid down-regulation observed with sibutramine HCl is not confined toβ-adrenoceptors alone, because pre- and postsynaptic α2-adrenoceptor function is also attenuated by 3 days of treatment with this novel antidepressant drug.

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  1. Boots Pharmaceuticals Research Department, NG2 3AA, Nottingham, UK

    David J. Heal, Michael R. Prow & W. Roger Buckett

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  1. David J. Heal
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  2. Michael R. Prow
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  3. W. Roger Buckett
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Heal, D.J., Prow, M.R. & Buckett, W.R. Effects of antidepressant drugs and electroconvulsive shock on pre- and postsynaptic α2-adrenoceptor function in the brain: rapid down-regulation by sibutramine hydrochloride. Psychopharmacology 103, 251–257 (1991). https://doi.org/10.1007/BF02244212

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  • DOI: https://doi.org/10.1007/BF02244212

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