[Induction by neuroleptics of certain genes in the central nervous system]

Prolonged administration of neuroleptic drugs increases the density of dopamine D2 receptors in several brain regions. We have recently shown that such treatment also raises dopamine D2 receptor mRNA levels in the striatum. To elucidate some of the initial events which lead to this upregulation, we studied the acute effects of dopamine D2 agonists and antagonists on the expression of c-jun and c-fos. A single injection I.P. of haloperidol (2 mg/kg) produced a rapid and transient increase in c-jun and c-fos mRNA in the rat striatum. This induction was specifically blocked by a D2 agonist (1 mg/kg quinelorane). In contrast, by itself quinelorane was without effect. These results show that dopamine D2 receptors inhibit the expression of a set of immediate early genes in the striatum, and these may be involved in the up-regulation of D2 mRNA upon prolonged neuroleptic treatment.