The role of dopamine in regulation of thyrotropin-releasing hormone in the striatum and nucleus accumbens of the rat.

The effect of alpha-methyl-p-tyrosine (alpha-MT), FLA-63, amphetamine, apomorphine and quinpirole on the concentration of thyrotropin-releasing hormone (TRH) in the striatum and nucleus accumbens was studied in rats. It has been found that the TRH content was increased in both those structures after alpha-MT, an inhibitor of tyrosine hydroxylase which reduced the concentration of both dopamine (DA) and noradrenaline (NA), but not after FLA-63, an inhibitor of DA-beta-hydroxylase which decreased the NA level without affecting DA. On the other hand, the indirectly acting dopaminomimetic amphetamine, the non-selective DA receptor agonist apomorphine, and the selective D2 receptor agonist quinpirole reduced the TRH level in the striatum, but not in the nucleus accumbens. Moreover, the decrease in the striatal peptide content induced by DA-mimetics was antagonized by the selective D2-receptor antagonist sulpiride, but not by the selective D1 receptor antagonist SCH 23390. The effect of amphetamine was not modified by the selective alpha 1-adrenoceptor antagonist prazosin. These results indicate that DA and D2 receptors play a significant role in the regulation of the striatal TRH.

Repeated treatment with amitriptyline or electroconvulsive shock does not affect thyrotropin releasing hormone receptors in discrete rat brain structures.

We studied the effect of repeated treatment with amitriptyline (10 mg/kg, p.o., twice daily for 14 days) or electroconvulsive shock (ECS) (once daily for 10 days) on the thyrotropin-releasing hormone (TRH) content and TRH receptors in the cerebral cortex, nucleus accumbens, striatum and septum of the rat. Repeated amitriptyline did not significantly affect the density or affinity of TRH receptors in the examined structures, but caused a marked increase in the TRH content in the striatum and nucleus accumbens. Long-term treatment with ECS reduced the density and affinity of TRH receptors in the septum only, but it increased the TRH concentration in the cerebral cortex and striatum. These results, together with the literature data, indicate that there is no simple relationship between the brain content (and release) of TRH and the functional sensitivity of TRH receptors on one hand, and the density of these receptors on the other.

Metabolic study of variation in plasma cholesterol level in normal men.

Variation in plasma cholesterol in normal populations underlies a 2-5 fold range of risk of coronary heart disease. The metabolic basis of this variation was studied in a healthy population recruited from a general-practice list. Compared with men in the modal decile of plasma cholesterol, those in the top decile maintained their high levels by overproduction of low-density lipoprotein (LDL). Men in the bottom decile of plasma cholesterol had low levels of LDL, resulting chiefly from a greater rate of fractional catabolism of this lipoprotein; and blood mononuclear cells from men in the bottom decile catabolised LDL more rapidly in vitro than did cells from other men. Intake of dietary lipids by men in the top, modal, and bottom deciles did not differ significantly. Different mechanisms appear to underlie high and low levels of plasma cholesterol in a normal population.