Effects of nicotine and chlorisondamine on cerebral glucose utilization inimmobilized and freely-moving rats

1 Chlorisondamine blocks central nicotinic receptors for many weeks via an unknown mechanism. Intracerebroventricular administration of [H-3]-chloriso ndamine in rats results in an anatomically restricted and persistent intrac ellular accumulation of radioactivity. The initial aim of the present study was to test whether nicotinic receptor antagonism by chlorisondamine is al so anatomically restricted. 2 Male adult rats were pretreated several times with nicotine to avoid the disruptive effects of the drug seen in drug-naive animals. They then receiv ed chlorisondamine (10 mu g i.c.v.) or saline, and local cerebral glucose u tilization (LCGU) was measured 4 weeks later after acute nicotine (0.4 mg k g(-1) s.c.) or saline administration. During testing, rats were partially i mmobilized. Nicotine significantly increased LCGU in the anteroventral thal amus and in superior colliculus. Chlorisondamine completely blocked the fir st of these effects. Chlorisondamine significantly reduced LCGU in the late ral habenula, substantia nigra pars compacta, ventral tegmental area, and c erebellar granular layer. 3 The second experiment was of similar design, but the rats were not pre-ex posed to nicotine, and were tested whilst freely-moving. Acute nicotine sig nificantly increased LCGU in anteroventral thalamus, superior colliculus, m edial habenula and dorsal lateral geniculate. Overall, however, nicotine si gnificantly decreased LCGU. Most or all of the central effects of nicotine on LCGU were reversed by chlorisondamine given 4 weeks beforehand. 4 These findings suggest that chlorisondamine blocks nicotinic effects wide ly within the brain. They also indicate that in freely-moving rats, nicotin e can reduce or stimulate cerebral glucose utilization, depending on the br ain area.