Depletion of cortical cholecystokinin levels after excitotoxin injection into the nucleus basalis: sensitivity to MK-801.
The release of cholecystokinin (CCK) in vitro has been shown to be influenced by NMDA receptors. In this study we have investigated whether excitotoxin-induced seizure activity affects the release and tissue content of CCK. Excitotoxin injection caused a significant decrease in CCK in ipsilateral frontal, parietal and temporal cortex by (30-54%) at 8 h compared to contralateral cortex and sham-operated controls and the effect was reversed by 24 h. No change was detected in occipital cortex, hippocampus and nucleus accumbens. The effect in frontal and temporal cortex was maximal at 8 h and could be completely prevented by treatment with MK-801(3 mg/kg i.p.). Anaesthesia (pentobarbital) alone or in combination with MK-801 did not affect peptide levels at 8 h. CCK mRNA levels were also studied quantitatively by slot-blot analysis but were unaffected at 6, 8 and 24 h after excitotoxin injection. The decrease in CCK tissue levels indicated that seizure activity stimulated CCK release which was confirmed in ex vivo experiments where K(+)-evoked (34 mM) CCK release was significantly enhanced in ipsilateral cerebral cortex at 6 h compared to contralateral cortex.
Bandopadhyay
R
R
Department of Biochemistry, Charing Cross and Westminister Medical School, London, UK.
De Belleroche
J
J
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D002766:Cholecystokinin / Q000235:genetics / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D015151:Immunoblotting; D007608:Kainic Acid / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D012640:Seizures / Q000139:chemically induced / Q000503:physiopathology*; D013701:Temporal Bone / Q000187:drug effects / Q000378:metabolism
D012333:RNA, Messenger; D016291:Dizocilpine Maleate; D002766:Cholecystokinin; D011188:Potassium; D007608:Kainic Acid