Regulation of cholecystokinin mRNA content in rat striatum: a glutamatergic hypothesis.
Changes in the cholecystokinin (CCK) mRNA content in rat striatum after the administration of specific glutamate and dopamine (DA) receptor agonists and antagonists were investigated. MK-801 (1 mg/kg i.p.), a selective noncompetitive N-methyl-D-aspartate (NMDA)-sensitive glutamatergic receptor antagonist, but not 6-cyano-7-nitroquinoxaline-2,3-dione (1.1-9.2 micrograms i.c.v.), a competitive non-NMDA glutamatergic receptor antagonist, produced a time- and dose-dependent decrease in striatal CCK mRNA. The maximum inhibition (50%) was observed after a daily treatment for 1 week with MK-801 (1 mg/kg). The activation of NMDA receptors by a single injection of NMDA (1.4 micrograms i.c.v.) elicited an 80% increase in CCK mRNA in rat striatum 8 hr after the injection. These data suggest that glutamate exerts a tonic regulation on striatal CCK mRNA, mainly through NMDA-sensitive glutamatergic receptors. B-HT 920, a DA D2 receptor agonist and benztropine, a DA uptake blocker, increased striatal CCK mRNA. This increase was partially blocked by the concomitant administration of MK-801. Moreover, the DA receptor antagonist haloperidol, at a dose that per se failed to change CCK mRNA (0.3 mg/kg i.p.), partially blocked the increase in CCK mRNA elicited by NMDA. Similarly, the NMDA effect was attenuated in rats with a 6-hydroxydopamine-induced nigrostriatal lesion. Our findings suggest that in rat striatum a complex DA-glutamate interaction tonically regulates CCK expression via D2 and/or NMDA receptor activation.
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Fidia-Georgetown Institute for the Neurosciences, Georgetown University, School of Medicine, Washington, DC 20007.
Mocchetti
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D000818:Animals; D002766:Cholecystokinin / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D015342:DNA Probes; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D004347:Drug Interactions; D006220:Haloperidol / Q000494:pharmacology; D007274:Injections, Intraperitoneal; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D015347:RNA Probes; D051381:Rats; D017207:Rats, Sprague-Dawley
D015342:DNA Probes; D015347:RNA Probes; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D002766:Cholecystokinin; D006220:Haloperidol