Pharmacological profile of nicotinic acetylcholine receptors in the rat prefrontal cortex: an electrophysiological study in a slice preparation.
The specificity of nicotinic receptors in the neocortex has been questioned previously because: (i) electrophysiological responses to nicotine could not be blocked by nicotinic antagonists, and (ii) the effect of nicotine was not mimicked by acetylcholine. In the present study, the presence of functional nicotinic receptors in rat neocortex has been assessed in a slice preparation of prefrontal cortex, using evoked field potential and unit recordings. Nicotine and the nicotinic agonists, dimethylphenylpiperazinium, cytisine, acetylthiocholine, applied by iontophoresis, produced an increase in the negative wave of field potentials, reflecting an increased excitability of cortical neurons. This effect was blocked by the selective probe for neuronal nicotinic receptors Toxin F (1.4 microM in the perfusion medium) and by dihydro-beta-erythroidine (100 microM). Alpha-bungarotoxin, the blocker of skeletal muscle acetylcholine receptor had no effect. Iontophoretically applied acetylcholine, muscarine and pilocarpine, on the other hand, produced a decrease in the field potential amplitude, which was blocked by atropine and scopolamine (1-10 microM). In the presence of eserine (10 microM), the muscarinic effect of acetylcholine was dramatically altered, leading to the development of a nicotinic response sensitive to Toxin F. Thus, the physiological activation of nicotinic receptors in rat prefrontal cortex appears to require higher concentrations of acetylcholine than do muscarinic receptors. Our results show that: (i) the rat prefrontal cortex possesses functional nicotinic receptors with a pharmacological profile clearly distinct from muscle receptors, and (ii) a nicotinic effect of acetylcholine can be revealed when its degradation by acetylcholinesterase is inhibited.
Vidal
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URA CNRS 0210, Département des Biotechnologies, Institut Pasteur, Paris, France.
Changeux
J P
JP
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology*; D030162:Reptilian Proteins; D012910:Snake Venoms / Q000494:pharmacology
D009498:Neurotoxins; D011978:Receptors, Nicotinic; D030162:Reptilian Proteins; D012910:Snake Venoms; C041907:snake venom neurotoxin F; D009538:Nicotine; D002217:Carbachol; D000109:Acetylcholine