Chronic treatment with some atypical antidepressants increases the brain level of 3-methoxy-4-hydroxyphenylglycol (MHPG) in rats

We examined the effects of some atypical antidepressants with central antiserotonergic activity (mianserin, trazodone, danitracen, pizotifen), and 5-HT receptor blocking agents (cyproheptadine and metergoline), on whole rat brain levels of the main noradrenaline (NA) metabolite, 3-methoxy-4-hydroxyphenylglycol (MHPG). In acute experiments, when drugs were injected in a single dose 1, 2, 4, 24 or 48 h before decapitation, only mianserin elevated the MHPG level. In chronic experiments (drugs given b. i. d. for 3 weeks, the last dose being given 4 or 48 h before decapitation), all the drugs significantly increased the concentration of whole brain MHPG. The results indicate that chronic administration of atypical antidepressants leads to activation of the central NA system. It seems, with the exception of mianserin, that this is a secondary phenomenon, resulting from the antiserotonergic activity of the drugs. Our results further corroborate the existence of a serotonergic-noradrenergic interaction, consisting of an inhibitory influence of serotonin on the noradrenergic system.