Dopamine D-1- and D-2-dependent catalepsy in the rat requires functional NMDA receptors in the corpus striatum, nucleus accumbens and substantia nigra pars reticulata

Abstract

This study investigated the anticataleptic activity of MK-801 versus the D-1 antagonist SCH 23390 and the D-2 antagonist raclopride, using the horizontal bar test in the rat. MK-801, 0.2 mg/kg i.p., strongly opposed the cataleptogenic actions of SCH 23390 and raclopride administered systemically (1 and 3 mg/kg i.p., respectively), or directly into the corpus striatum (CS) or nucleus accumbens (NAc; 1 and 10 mu g, respectively). Conversely, intraCS and intraNAc pretreatment with MK-801 (10 mu g) markedly attenuated the cataleptic response to a systemic injection of SCH 23390 or raclopride. In the latter experiments the anticataleptic effect of MK-801 was pronounced and sustained(>2 h), except with intraCS MK-801 versus raclopride, where it was initially profound but only short-lived (15 min). Stereotaxic injection of MK-801 (1 mu g) into the substantia nigra pars reticulata (SNr) prevented catalepsy developing to either dopamine D-1 or D-2 receptor antagonism. These results indicate there must be unimpeded glutamate neurotransmission in the CS and NAc before catalepsy can develop fully to D-1 and D-2 dopamine receptor blockade in these structures. The weaker glutamate-D-2 interaction in the CS than in the NAc may be related to differences in the N-methyl-D-aspartate receptor subpopulations in these nuclei. Finally, the ability of intranigral MK-801 to diminish both D-1- and D-2-dependent catalepsy suggests the SNr acts as a common output pathway for the expression of both forms of catalepsy in the rat. (C) 1997 Elsevier Science B.V.