Effects of YM-43611, a novel dopamine D2-like receptor antagonist, on immediate early gene expression in the rat forebrain.
The pharmacological characteristics of two benzamides, YM-43611, a potent and selective dopamine D3 and D4 antagonist, and YM-09151-2 (nemonapride), were compared with two reference antipsychotic agents, haloperidol and clozapine, in terms of modification of c-fos and related gene expression in the rat forebrain. After subcutaneous injection of YM-43611 (1 or 5 mg/kg), nemonapride (4 mg/kg), haloperidol (1 mg/kg), or clozapine (25 mg/kg), Fos immunocytochemistry was employed, and the distributions of Fos-like immunoreactive neurons were compared. As was the case for the two reference antipsychotics, the two benzamides enhanced c-Fos immunoreactivity in a number of forebrain regions. Specifically, like clozapine and nemonapride, YM-43611 significantly increased the number of immunoreactive cells in the nucleus accumbens shell and islands of Calleja. In contrast to clozapine and nemonapride, YM-43611 did not increase c-fos expression in the medial prefrontal cortex. Haloperidol and nemonapride elevated the number of positive cells in the striatum and nucleus accumbens core, whereas clozapine and YM-43611 did not. Clozapine increased the number of Fos-like immunoreactive cells in the lateral septal nucleus and the diagonal band nucleus, but YM-43611, nemonapride, and haloperidol did not. The present findings demonstrate that in comparison with three other drugs, YM-43611 has restricted effects on c-fos expression in the rat forebrain and is active primarily in the shell region of the nucleus accumbens and the islands of Calleja. The ability of YM-43611 to block D3 and D4 receptors may contribute to its unique actions on Fos induction.
Kurokawa
K
K
Department of Psychiatry, Shiga University of Medical Science, Otsu, Japan.
Narita
M
M
Koshiya
K
K
Hidaka
K
K
Ohmori
J
J
Satoh
K
K
D000818:Animals; D001549:Benzamides / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology; D007150:Immunohistochemistry; D008297:Male; D016548:Prosencephalon / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects*
D001549:Benzamides; D018492:Dopamine Antagonists; C100801:N-(1-benzyl-3-pyrrolidinyl)-5-chloro-4-((cyclopropylcarbonyl)amino)-2-methoxybenzamide; D016760:Proto-Oncogene Proteins c-fos; D017448:Receptors, Dopamine D2; D003024:Clozapine; D006220:Haloperidol; C030265:nemonapride