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.