Dopamine D1- and D2-dependent catalepsy in the rat requires functional NMDA receptors in the corpus striatum, nucleus accumbens and substantia nigra pars reticulata

This study investigated the anticataleptic activity of MK-801 versus the D₁ antagonist SCH 23390 and the D₂ 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 μg, respectively). Conversely, intraCS and intraNAc pretreatment with MK-801 (10 μg) 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 μg) into the substantia nigra pars reticulata (SNr) prevented catalepsy developing to either dopamine D₁ or D₂ receptor antagonism. These results indicate there must be unimpeded glutamate neurotransmission in the CS and NAc before catalepsy can develop fully to D₁ and D₂ dopamine receptor blockade in these structures. The weaker glutamate–D₂ interaction in the CS than in the NAc may be related to differences in the N-methyl-

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-aspartate receptor subpopulations in these nuclei. Finally, the ability of intranigral MK-801 to diminish both D₁- and D₂-dependent catalepsy suggests the SNr acts as a common output pathway for the expression of both forms of catalepsy in the rat.