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 α2-adrenoceptor agonist, clonidine (250 μg/kg, i.p.) on thyrotropin (TSH) secretion in the rat, but did not alter basal TSH secretion. β-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 μg/kg, i.v.) on TSH release and its inhibition by the α-adrenoceptor antagonist, phentolamine (2 mg/kg, i.p.). These findings suggest that chronic desipramine treatment induces subsensitivity of α2-adrenoceptors which modulate TSH secretion in the rat while not affecting β2-adrenoceptor-mediated inhibition of TSH release. These findings suggest that pituitary TRH receptors are unchanged but that changes occurred at the hypothalamic level in α2-adrenoceptor-mediated stimulation of TRH release. Although cerebral β-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.