alpha 2-Adrenoreceptors in rat brain are decreased after long-term tricyclic antidepressant drug treatment.
After two weeks of twice-daily administration of amitriptyline to rats, the binding of [3H]clonidine to presynaptic alpha 2-adrenoreceptors was decreased in membranes isolated from 5 areas of the rat brain. After one day of treatment, binding did not differ from saline treated controls. In vitro, a high concentration of amitriptyline caused a competitive inhibition of [3H]clonidine binding but did not alter the number of binding sites. The decrease in the number of alpha 2-adrenoreceptor binding sites after two weeks of amitriptyline treatment would explain the subsensitivity of these receptors which occurs after prolonged administration of antidepressant drugs.
D000639:Amitriptyline / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D003000:Clonidine / Q000378:metabolism*; D007700:Kinetics; D009928:Organ Specificity; D051381:Rats; D011941:Receptors, Adrenergic / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism*
D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D000639:Amitriptyline; D003000:Clonidine