Regional Effects of NMDA Receptor Antagonists on the Induction of Striatal c-fos by Fenfluramine.
Induction of the immediate early gene c-fos occurs in striatal nerve cells in response to psychotropic drugs affecting the dopaminergic system. Although this nuclear induction is mediated in part through D(1) receptors, the involvement of N-methyl-d-aspartate (NMDA)-sensitive receptors has been also demonstrated. In the experiments reported here, we examined the effects of the noncompetitive NMDA receptor antagonists ketamine (2 mg/kg; as an anesthetic mixture) and dizocilpine (MK-801; 1 mg/kg), as well as the competitive NMDA receptor antagonist, 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP; 5 mg/kg), on the expression of fos-like protein induced by dl-fenfluramine (20 mg/kg), in the rat caudate putamen. Systemic (IP) administration of the above receptor antagonists 30 min prior to fenfluramine exposure resulted in the blockade of c-fos immunoreactivity. Although the ketamine mixture totally abolished the expression of the immediate early gene, MK-801 and CPP only partially blocked such expression. In addition, pretreatment with the D(1) receptor antagonist SCH 23390 (0.5 mg/kg) also partially suppressed the induction of c-fos by fenfluramine. These findings suggest the participation of NMDA as well as dopamine-sensitive receptors for the induction of striatal c-fos by an indirect serotonergic (5-HT) agonist. The significance of these results is discussed in terms of a possible glutamatergic and dopaminergic mechanism.
Torres
G
G
The Clayton Foundation Laboratories for Peptide Biology, The Salk Institute, 10010 North Torrey Pines Road, La Jolla, California 92037.
Rivier
C
C