MK 801 reverses haloperidol-induced catalepsy from both striatal and extrastriatal sites in the rat brain.
The present study investigated whether the anticataleptic effect of (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)-cyclohepten-5,10-imine (MK 801) is due to a blockade of N-methyl-D-aspartate (NMDA) receptors in striatal output pathways as well as in the striatum. Catalepsy induced by haloperidol (1 mg/kg i.p.) was more effectively reversed by MK 801 (0.2 mg/kg i.p.) given 10 min prior to rather than 45 min after the neuroleptic. Catalepsy evoked by intrastriatal haloperidol (7 micrograms/side) was also strongly attenuated by systemic MK 801 (0.2 mg/kg i.p.). We also found that the cataleptic rigidity induced by systemic haloperidol (1 mg/kg i.p.) could be prevented by prior injection of MK 801 into the striatum (10 micrograms), subthalamic nucleus (5 micrograms), entopeduncular nucleus (5 micrograms) or substantia nigra pars reticulata (1 microgram). These results suggest that the anticataleptic action of systemic MK 801 versus haloperidol, is due to the blockade of NMDA receptors in the striatum as well as in striatal output circuits through the subthalamus. However, systemic MK 801 (0.2 mg/kg i.p.) was without effect on the catalepsy elicited by injecting muscimol into the globus pallidus (25 ng) or ventromedial thalamus (50 ng). These findings suggest that MK 801 has little influence over thalamic excitatory feedback to the cortex, and that hypoactivity of the pallidum may not be a prerequisite for hyperactivity in the subthalamus.
Kaur
S
S
Department of Pharmacology, School of Pharmacy, London, UK.
Ozer
H
H
Starr
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005917:Globus Pallidus / Q000187:drug effects / Q000378:metabolism; D006220:Haloperidol; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013788:Thalamus / Q000187:drug effects / Q000378:metabolism
D014150:Antipsychotic Agents; D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D009118:Muscimol; D016291:Dizocilpine Maleate; D006220:Haloperidol