Effects of ZK 93426 on muscarinic and nicotinic antagonist or nucleus basalis lesioning-induced electrocortical slowing.
The present study investigated the effects of a benzodiazepine receptor antagonist, beta-carboline ZK 93426 (1, 3 and 10 mg/kg, IP), on scopolamine and nucleus basalis (NB) quisqualic acid lesion-induced neocortical electrocortical activity slowing in rats. Scopolamine induced a dose dependent increase in EEG spectral values and slow delta waves (0.3 < 0.9 = 2.7 mg/kg IP). ZK 93426 partially reversed EEG slowing induced by the smallest scopolamine dose (0.3 mg/kg), but had no effect on the EEG changes induced by higher doses. A combination of scopolamine at 0.3 mg/kg and mecamylamine (a centrally active nicotinic antagonist) at 10 mg/kg induced an EEG slowing that was not reversed by ZK 93426. NB lesions markedly decreased cortical choline acetyltransferase (ChAT) activity (-77%) and increased EEG slow waves. ZK 93426 had no effect on the NB lesion-induced slow wave activity increase. The present results support the idea that beta-carboline ZK 93426 may increase cortical cholinergic activity by disinhibiting the NB cholinergic neurons. However, if the activity of "NB to cortex" cholinergic system is greatly decreased by either a marked reduction in NB cell number (in NB-lesioned rats), a near complete cortical post-synaptic muscarinic receptor blockade (large scopolamine dose) or by a combination of nicotinic (decrease acetylcholine release) and muscarinic receptor blockade, the effects of beta-carboline ZK 93426 on EEG slowing may be negligible.
Riekkinen
P
P
University of Kuopio, Department of Neurology, Finland.
Riekkinen
M
M
Sirviö
J
J
Riekkinen
P
P
D000818:Animals; D001479:Basal Ganglia / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology*; D002243:Carbolines / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000033:anatomy & histology / Q000502:physiology*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography / Q000187:drug effects*; D058787:GABA-A Receptor Antagonists; D008297:Male; D008464:Mecamylamine / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012601:Scopolamine / Q000494:pharmacology
D002243:Carbolines; D058787:GABA-A Receptor Antagonists; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D008464:Mecamylamine; C042568:ZK 93426; D016318:Quisqualic Acid; D012601:Scopolamine; D002795:Choline O-Acetyltransferase