Modulation by antidepressant drugs of CNS postsynaptic alpha 2-adrenoceptors mediating mydriasis in the rat.
The modulation of central postsynaptic alpha 2-adrenoceptors mediating mydriasis in the pentobarbitone-anaesthetized rat was studied after the acute and short/long-term administration of antidepressant treatments (drugs, electroshock). The acute administration of cyclic antidepressant drugs (2.5 mg/kg, i.v.) resulted in different mydriatic effects (amitriptyline greater than protriptyline approximately imipramine greater than clomipramine greater than nortriptyline greater than desipramine approximately maprotiline) which were attenuated (17-55%) by idazoxan (1 mg/kg, i.v., 5 min) and reserpine (5 mg/kg, s.c., 18 h) indicating that, besides the well-known anticholinergic properties of some of these drugs, their mydriatic effects are due in part to activation of alpha 2-adrenoceptors (through endogenous noradrenaline). In contrast, the long-term (7-21 days) but not the short-term (1-4 days) administration of cyclic antidepressant drugs (2.5-10 mg/kg, i.p.), MAO inhibitors (1 mg/kg, i.p.), lithium (20 mg/kg, i.p.) and electroshock (150 mA, 63 Hz, 8 ms during 300 ms) resulted in dose- and time-dependent reductions of the dose-pupillary response curve for clonidine (ED50 increased 1.2-2.0-fold; Emax decreased by 9-29%) which indicated desensitization of postsynaptic alpha 2-adrenoceptors. In line with these findings, treatment for 7 days with clonidine (0.1-1 mg/kg, i.p.) or idazoxan (3-10 mg/kg, i.p.) led to an opposite modulation (down- and up-regulation) of the dose-pupillary response curve for clonidine. The main results demonstrate that cyclic antidepressant drugs, through indirect mechanisms which involve endogenous noradrenaline, can modulate the sensitivity of brain postsynaptic alpha 2-adrenoceptors mediating mydriasis in the rat.
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Departamento de Investigación, S.A. Lasa Laboratorios, Barcelona, Spain.
Obach
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García-Sevilla
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D000758:Anesthesia; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D002490:Central Nervous System / Q000187:drug effects / Q000502:physiology*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D004597:Electroshock; D019329:Idazoxan; D008297:Male; D009184:Mydriatics; D011680:Pupil / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
D000928:Antidepressive Agents; D004146:Dioxanes; D009184:Mydriatics; D011942:Receptors, Adrenergic, alpha; D003000:Clonidine; D019329:Idazoxan