Chronic Depletion of Brain Catecholamines and Thyrotropin Secretion in the Rat

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Abstract
Basal and cold-stimulated TSH [thyrotropin] plasma levels were measured in rats adapted to warmth after chronic depletion of brain norepinephrine (NE) by 6-hydroxydopamine (6-OHDA). Injection into the third ventricle of 6-OHDA (50 .mu.g) produced a significant decrease of hypothalamic NE 1, 3, 15 and 30 days after the treatment without modifying basal plasma TSH levels. The acute release of TSH evoked by cold exposure (CE) was abolished by 6-OHDA only 24 h later, while 3, 15, 30 days later, despite sharply decreased hypothalamic NE, no significant inhibition of CE-stimulated TSH secretion was detectable. Pretreatment, 1 h before CE, with a dose of .alpha.-methyl-p-tyrosine (.alpha.-MpT; 75 mg/kg i.p.) ineffective in saline-preinjected animals, completely prevented the rise of plasma TSH in rats injected with 6-OHDA in the third ventricle 30 days earlier. These results suggest that some time after the degeneration of catecholamine (CA) terminals there remains in the hypothalamus a small pool of NE responsible for the stimulation of TRH secretion. The .alpha.-adrenergic agonist clonidine, injected intraventricularly in rats pretreated 30 days earlier with 6-OHDA, caused a significant rise of basal TSH levels at 10 and 30 min after the injection, whereas in control animals the drug caused an increase of the basal level of TSH 30 but not 10 min after the treatment. At 30 min the increase was statistically higher in 6-OHDA than in saline-pretreated rats. The i.p. administration of clonidine completely restored the TSH response to cold abolished by a large dose of .alpha.-MpT (250 mg/kg i.p.) in rats treated 30 days earlier with 6-OHDA, whereas clonidine only partially restored the response in animals preinjected with saline. The results support the suggestion that the NE post-synaptic receptors involved in TRH secretion become supersensitive following functional denervation with 6-OHDA.