Effects of chronic risperidone on central noradrenergic transmission

In the present work, we investigated the effects of chronic risperidone adm inistration on the activity of locus coeruleus noradrenergic neurons. In ad dition, the effect of chronic risperidone administration on the basal level of norepinephrine in the prefrontal cortex was evaluated. Results of this research showed that chronic risperidone administration increased the activ ity of locus coeruleus noradrenergic neurons. The sensitivity of alpha(2)-a drenoceptors in the somatodendritic region of the locus coeruleus was asses sed by using the ID50 of clonidine. Results indicated that the firing rate of locus coeruleus noradrenergic neurons was the same in risperidone-treate d rats and controls. Similarly, the ID50 for (+/-)-2,5-dimetoxy-4-iodoamphe tamine (DOI), an agonist of 5-HT2 receptors which inhibits the activity of locus coeruleus neurons by acting on these receptors, did not show any diff erences between the firing rate of these neurons in risperidone treated rat s and controls. Unlike controls, chronically treated rats showed a signific ant decrease in norepinephrine levels in the prefrontal cortex. The decreas ed release of norepinephrine following continuous risperidone administratio n could be explained by the sustained increase in locus coeruleus neuronal activity after chronic risperidone administration. This low norepinephrine level in the prefrontal cortex may contribute to the relief of certain nega tive schizophrenic symptoms and to the improvement of cognitive function. ( C) 2000 Elsevier Science B.V. All rights reserved.