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.

Chronic treatment with antidepressants: protentiation of clonidine-induced aggression in mice via noradrenergic mechanism.

The chronic (10 mg/kg i.p. twice daily, 10 days)-and not the acute-administration of amitriptyline, maprotiline or zimelidine enhances aggressiveness induced by clonidine in mice. An analogous potentiation of clonidine-induced aggressiveness was obtained with chronic administration (the schedule as above) of levomepromazine (2 mg/kg) or thioridazine (5 mg/kg) but not of spiperone (0.2 mg/kg). Fluoxetine (10 mg/kg), atropine (5 mg/kg), propranolol (10 mg/kg) or metergoline (0.5 mg/kg) given chronically (the schedule as above) also had no effect. The enhancement of clonidine aggressiveness induced by prolonged treatment with imipramine (10 mg/kg) was prevented by cycloheximide, an inhibitor of protein synthesis. The results supply further evidence for the previously proposed hypothesis that chronic administration of antidepressants enhances the responsiveness of central postsynaptic noradrenaline receptors.

Effects of chronic administration of antidepressant drugs on aggressive behavior induced by clonidine in mice.

The effects of antidepressant drugs on clonidine-induced aggressive behavior were determined in mice. Imipramine, mianserin and iprindole used in a single dose attenuated clonidine-induced aggression. Their chronic administration enhanced it.