Functional supersensitivity of CNS alpha 1-adrenoceptors following chronic antidepressant treatment.
Chronic but not acute administration (21 days) of desipramine (10 mg/kg), amitriptyline (10 mg/kg) or iprindole (5 mg/kg) enhanced the stimulatory effect of the alpha 1-adrenergic agonist phenylephrine on the acoustic startle reflex when phenylephrine was infused into the subarachnoid space of the spinal cord. Comparable supersensitivity to phenylephrine also occurred 1 week after selective depletion of norepinephrine in the spinal cord via intrathecal administration of 6-hydroxydopamine. Behavioral supersensitivity to phenylephrine was associated with an increase in the number of 3H-prazosin binding sites following denervation but not following chronic antidepressant treatments. The results indicate that chronic antidepressant treatments may enhance functional alpha 1-adrenergic transmission through mechanisms different than those following denervation.
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001665:Binding Sites; D003891:Desipramine / Q000494:pharmacology; D006892:Hydroxydopamines / Q000494:pharmacology; D007488:Iprindole / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D016627:Oxidopamine; D010656:Phenylephrine / Q000494:pharmacology; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D012022:Reflex, Acoustic / Q000187:drug effects
D000928:Antidepressive Agents; D006892:Hydroxydopamines; D011941:Receptors, Adrenergic; D011942:Receptors, Adrenergic, alpha; D000639:Amitriptyline; D010656:Phenylephrine; D007488:Iprindole; D016627:Oxidopamine; D003891:Desipramine; D009638:Norepinephrine; D011224:Prazosin