title: Nicotinic and muscarinic receptor-evoked depolarizations recorded from a novel cortical brain slice preparation.
abstract: We have developed a novel cortical brain slice preparation for extracellular field-potential recording using the grease-gap barrier technique. This preparation allows the study of cholinergic and glutamatergic depolarization responses of neocortical pyramidal neurones whose axons pass through the corpus callosum to contralateral cortical areas. Concentration-effect curves to carbachol, 1,1-dimethyl-4-phenyl piperazinium (DMPP) and muscarine yielded mean EC50 values of 29.5, 13.2 and 17.7 microM, respectively. Carbachol-induced responses were antagonized by both atropine and mecamylamine in a manner consistent with agonist effects of carbachol at both nicotinic and muscarinic sites, while concentration-effect curves to DMPP and muscarine were shifted rightward in a parallel manner by mecamylamine (10 microM) and atropine (5 nM), with antagonist pKB estimates of 6.4 and 9.0, respectively. Depolarization responses to glutamate were reversibly antagonized by D-2-amino-5-phosphonopentanoic acid and 6-cyano-7-nitroquinoxaline-2,3-dione; these antagonists had no effect on carbachol or DMPP-induced responses. This preparation allows reproducible quantification of depolarization responses of pyramidal neurones forming the corticocortical pathway, and indicates the presence of functional nicotinic and muscarinic receptors. We conclude that the preparation is a convenient model with which to test the efficacy of cholinomimetic agents in an intact neocortical system, and may be useful in the development of novel drugs for the treatment of the cognitive symptoms of Alzheimer's disease.
authors.affiliation: Glaxo Institute of Applied Pharmacology, Department of Pharmacology, University of Cambridge, England.
authors.forename: I P
authors.initials: IP
authors.lastname: Chessell
authors.forename: P P
authors.initials: PP
authors.lastname: Humphrey
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D009116:Muscarine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*
chemical_list: D011976:Receptors, Muscarinic; D011978:Receptors, Nicotinic; D018698:Glutamic Acid; D004246:Dimethylphenylpiperazinium Iodide; D009116:Muscarine; D002217:Carbachol