Antidepressant treatment and chemical sympathectomy fail to modulate alpha 1-adrenoceptor sensitivity in mouse eye

The mydriatic response to alpha 1-adrenergic agonists was used as a functional index of postsynaptic alpha 1-adrenoceptors in mouse iris dilator muscle. Topical ocular application of methoxamine or phenylephrine caused dose-related mydriasis which was inhibited by pretreatment with prazosin or phentolamine. Chemical sympathectomy with topical 6-hydroxydopamine (6-OHDA) produced supersensitivity to phenylephrine but not methoxamine. Daily antidepressant treatment for 14 days with desipramine (10 mg/kg, i.p.), amitriptyline (10 mg/kg, i.p.), fluoxetine (2 mg/kg, i.p.), or moclobemide (40 mg/kg, i.p.) did not alter the response to methoxamine. Central alpha 1-adrenoceptors labelled with [3H]prazosin were similarly unaffected except for a modest downregulation produced by fluoxetine. These results demonstrate that postsynaptic alpha 1-adrenoceptors in mouse CNS and iris dilator muscle are refractory to manipulations known to alter their sensitivity in other tissues.