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.
Fawcett
J P
JP
School of Pharmacy, University of Otago, Dunedin, New Zealand.
Patel
P P
PP
Menkes
D B
DB
D000287:Administration, Topical; D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D020912:Moclobemide; D016627:Oxidopamine; D010646:Phentolamine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects* / Q000502:physiology; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D013563:Sympathectomy, Chemical; D013997:Time Factors
D000928:Antidepressive Agents; D001549:Benzamides; D018340:Receptors, Adrenergic, alpha-1; D005473:Fluoxetine; D000639:Amitriptyline; D010656:Phenylephrine; D016627:Oxidopamine; D008729:Methoxamine; D020912:Moclobemide; D003891:Desipramine; D011224:Prazosin; D010646:Phentolamine