The effect of (+/-)mianserin and its enantiomers on the behavioural hyperactivity of the olfactory-bulbectomized rat.

The effects of (+/-)mianserin and its enantiomers on the behavioural hyperactivity of the olfactory bulbectomized (OB) rat and on the levels of some central neurotransmitters were investigated. The reversal of hyperactivity by racemic mianserin was found to be independent of dose within a non-sedative range of 2-10 mg/kg and occurred following seven days of treatment. Chronic administration of racemic mianserin, over the dose range 2-15 mg/kg elevated the steady-state concentration of noradrenaline in the amygdaloid cortex and midbrain. Of the two enantiomers, only the behaviourally active (+)-(S)-form increased the steady state concentration of noradrenaline in these two areas of the brain. The reversal of the hyperactivity by (+/-)mianserin and the (+)-(S)-enantiomer was not associated with a change in the concentration of serotonin or 5-hydroxyindole acetic acid. The behaviourally inactive enantiomer (-)-(R) decreased the concentration of 5-hydroxyindole acetic acid, an effect which may be associated with the sedative action of the drug. The results suggest that the reversal of the behavioural hyperactivity of the olfactory bulbectomized (OB) rat by (+/-)mianserin and its (+)-(S)-enantiomer is associated with an increase in the steady-state concentration of noradrenaline, in the areas of the brain studied.