Effects of nicotine and chlorisondamine on cerebral glucose utilization in immobilized and freely-moving rats.
Chlorisondamine blocks central nicotinic receptors for many weeks via an unknown mechanism. Intracerebroventricular administration of [(3)H]-chlorisondamine in rats results in an anatomically restricted and persistent intracellular accumulation of radioactivity. The initial aim of the present study was to test whether nicotinic receptor antagonism by chlorisondamine is also anatomically restricted. Male adult rats were pretreated several times with nicotine to avoid the disruptive effects of the drug seen in drug-naïve animals. They then received chlorisondamine (10 microg i. c.v.) or saline, and local cerebral glucose utilization (LCGU) was measured 4 weeks later after acute nicotine (0.4 mg kg(-1) s.c.) or saline administration. During testing, rats were partially immobilized. Nicotine significantly increased LCGU in the anteroventral thalamus and in superior colliculus. Chlorisondamine completely blocked the first of these effects. Chlorisondamine significantly reduced LCGU in the lateral habenula, substantia nigra pars compacta, ventral tegmental area, and cerebellar granular layer. The second experiment was of similar design, but the rats were not pre-exposed to nicotine, and were tested whilst freely-moving. Acute nicotine significantly increased LCGU in anteroventral thalamus, superior colliculus, medial habenula and dorsal lateral geniculate. Overall, however, nicotine significantly decreased LCGU. Most or all of the central effects of nicotine on LCGU were reversed by chlorisondamine given 4 weeks beforehand. These findings suggest that chlorisondamine blocks nicotinic effects widely within the brain. They also indicate that in freely-moving rats, nicotine can reduce or stimulate cerebral glucose utilization, depending on the brain area. British Journal of Pharmacology (2000) 129, 147 - 155
Marenco
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T
Department of Pharmacology and Therapeutics, McGill University, 3655 Drummond Street, Montreal H3G 1Y6, Canada.
Bernstein
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S
Cumming
P
P
Clarke
P B
PB
D000818:Animals; D000963:Antimetabolites; D001345:Autoradiography; D001923:Brain Chemistry / Q000187:drug effects*; D002714:Chlorisondamine / Q000494:pharmacology*; D003847:Deoxyglucose; D005947:Glucose / Q000378:metabolism*; D007103:Immobilization; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000963:Antimetabolites; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D009538:Nicotine; D003847:Deoxyglucose; D005947:Glucose; D002714:Chlorisondamine