Sensitivity of rat frontal cortical neurones to nicotine is increased by chronic administration of nicotine and by lesions of the nucleus basalis magnocellularis: comparison with numbers of [3H]nicotine binding sites.
The effects of chronic nicotine treatment and of unilateral AMPA lesion of the nucleus basalis magnocellularis (nbm) on the sensitivity of frontal cortical neurones to iontophoretically applied nicotine were studied. Chronic nicotine treatment increased the number of [3H]nicotine binding sites from 2.9 to 3.9 pmol g-1 wet weight, and increased the proportion of cortical neurones responding to nicotine from 32.3% to 60.0%. After unilateral nbm lesions, the densities of AChE-positive fibers and [3H]nicotine binding sites were reduced by approximately 97% and 55%, respectively, and the proportion of neurones responding to nicotine increased from 32.3% to 53.8%. The two treatments, chronic nicotine administration and nbm lesion, also increased the size of individual neuronal responses, prolonged their duration, and shortened the response latency. Responses to glutamate were unaffected by either procedures. The results show that the increase in [3H]nicotine binding produced by chronic nicotine administration is associated with an increased response to iontophoretically applied nicotine, suggesting that the receptor upregulation induced by the chronic treatment were functional. Less easily explained is the association between increased sensitivity of frontal cortical neurons to nicotine after nbm lesion with a decreased receptor density. It is suggested that a substantial proportion of nicotinic receptors are located presynaptically, and that their loss after lesion concealed an upregulation at postsynaptic sites.
Abdulla
F A
FA
Department of Pharmacology, University of Alberta, Edmonton, Canada.
Calaminici
M
M
Wonnacott
S
S
Gray
J A
JA
Sinden
J D
JD
Stephenson
J D
JD
D000818:Animals; D001665:Binding Sites; D005625:Frontal Lobe / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D018698:Glutamic Acid / Q000494:pharmacology; D008297:Male; D009474:Neurons / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013377:Substantia Innominata / Q000502:physiology*; D013997:Time Factors; D014316:Tritium
D014316:Tritium; D018698:Glutamic Acid; D009538:Nicotine