Nicotinic agonists modulate basal forebrain control of cortical cerebral blood flow in anesthetized rats.
Previous studies have indicated that electrical microstimulation of the cholinergic (basal forebrain, BF) elicits profound increases in cortical cerebral blood flow (CBF) that are selectively attenuated by nicotinic receptor antagonists. This study sought to determine whether nicotinic receptor agonists such as (-)-nicotine, and related agents, can enhance the increases in CBF elicited by electrical stimulation of the BF of urethane-anesthetized rats. The magnitude of cortical CBF responses, measured by laser-Doppler flowmetry, increased progressively with higher frequencies (range = 6.25-50 Hz) to a maximum of 248% of control. (-)-Nicotine and (-)-lobeline each further enhanced the responses to BF stimulation, with (-)-nicotine having the most potent effect (up to 350%). (+)-Nicotine and (-)-cotinine were without effect, suggesting stereoselectivity and that the effects were not mediated by the major metabolite of (-)-nicotine. In contrast, (-)-cystisine, another nicotinic receptor agonist, modestly inhibited the BF-elicited increase in CBF suggesting nicotinic receptor subtype selectivity in mediating the response. Arecoline, a potent muscarinic agonist, was without effect suggesting that muscarinic mechanisms are not involved in the mediation of this response. None of the nicotinic agents had overt effects on heart rate or blood pressure in the dose ranges examined. In experiments targeting the site of action of the nicotinically mediated enhancement, (-)-nicotine microinjections into the BF elicited profound increases in cortical CBF, whereas similar injections into the cerebral cortex were without effect suggesting that nicotine receptors mediating CBF increases are localized to the BF.(ABSTRACT TRUNCATED AT 250 WORDS)
Linville
D G
DG
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield.
Williams
S
S
Raszkiewicz
J L
JL
Arneric
S P
SP
D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001392:Azocines; D001794:Blood Pressure / Q000187:drug effects; D002540:Cerebral Cortex / Q000098:blood supply; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D005971:Glutamates / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D007275:Injections, Intravenous; D008120:Lobeline / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011807:Quinolizines; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012039:Regional Blood Flow / Q000187:drug effects; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D005971:Glutamates; D008120:Lobeline; D009538:Nicotine; D010277:Parasympathomimetics; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids