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 microg, respectively). Conversely, intraCS and intraNAc pretreatment with MK-801 (10 microg) 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 microg) 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-D-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.
Ozer
H
H
Department of Pharmacology, Faculty of Pharmacy, University of Istanbul, Beyazrt Istanbul, Turkey.
Ekinci
A C
AC
Starr
M S
MS
D000818:Animals; D001552:Benzazepines / Q000494:pharmacology; D001923:Brain Chemistry / Q000502:physiology*; D002375:Catalepsy / Q000139:chemically induced / Q000503:physiopathology*; D003342:Corpus Striatum / Q000737:chemistry / Q000503:physiopathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009714:Nucleus Accumbens / Q000737:chemistry / Q000503:physiopathology; D020891:Raclopride; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000502:physiology*; D017448:Receptors, Dopamine D2 / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012457:Salicylamides / Q000494:pharmacology; D013378:Substantia Nigra / Q000737:chemistry / Q000503:physiopathology
D001552:Benzazepines; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D012457:Salicylamides; D020891:Raclopride; D016291:Dizocilpine Maleate