Enhancement of brain noradrenaline and dopamine turnover by thyrotropin-releasing hormone and its analogue NS-3 in mice and rats

The effects of intravenous injections of thyrotropin-releasing hormone and its analog NS-3 (montirelin hydrate, CG3703) on the dynamics of brain monoamines were examined in mice and rats. In mice, both NS-3 (0.1-1 mg/kg) and thyrotropin-releasing hormone (10 and 30 mg/kg) increased the concentrations of 4-hydroxy-3-methoxyphenylglycol, 3, 4-dihydroxyphenylacetic acid and homovanillic acid. The turnover rates, estimated either by depletion of catecholamines after treatment with alpha-methyl-p-tyrosine or by probenecid-induced accumulation of homovanillic acid, were enhanced by these peptides. In contrast, none of the compounds had any influence on the serotonin turnover. In rats, both NS-3 and thyrotropin-releasing hormone produced a regionally specific increase in the concentrations of the catecholamine metabolites. A microdialysis study demonstrated that NS-3 significantly increased the release of dopamine in the nucleus accumbens as well as the striatum of conscious rats, while thyrotropin-releasing hormone caused a weak but significant enhancement of dopamine release only in the nucleus accumbens. These findings indicate that NS-3 was far more potent than thyrotropin-releasing hormone in facilitating the turnover of catecholamines without affecting serotonin turnover in the mouse and rat brain.