Effect of chronic desipramine treatment on neurotransmitter-thyrotropin releasing hormone--thyrotropin interactions in the rat.
Long-term administration of the antidepressant drug, desipramine (20 mg/kg/day, orally for 28 days), decreased the stimulatory effect of the alpha 2-adrenoceptor agonist, clonidine (250 micrograms/kg, i.p.) on thyrotropin (TSH) secretion in the rat, but did not alter basal TSH secretion. beta-Adrenoceptor-mediated inhibition of TSH secretion by isoproterenol (1 mg/kg, i.p.) was unaffected by chronic desipramine treatment, as were the stimulatory effect of TSH-releasing hormone (TRH, 5 micrograms/kg, i.v.) on TSH release and its inhibition by the alpha-adrenoceptor antagonist, phentolamine (2 mg/kg, i.p.). These findings suggest that chronic desipramine treatment induces subsensitivity of alpha 2-adrenoceptors which modulate TSH secretion in the rat while not affecting beta-adrenoceptor-mediated inhibition of TSH release. These findings suggest that pituitary TRH receptors are unchanged but that changes occurred at the hypothalamic level in alpha 2-adrenoceptor-mediated stimulation of TRH release. Although cerebral beta-adrenoceptors have been shown convincingly to be down-regulated after chronic desipramine treatment, their function in the hypothalamic TRH system after 28 days of treatment with desipramine appears to be unimpaired.
D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology*; D004347:Drug Interactions; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D010646:Phentolamine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000502:physiology*; D013972:Thyrotropin / Q000097:blood / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D011941:Receptors, Adrenergic; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D007545:Isoproterenol; D003000:Clonidine; D003891:Desipramine; D010646:Phentolamine