We used the autoradiographic 2-deoxy-D-[1-14C]glucose (14C-DG) method of Sokoloff to identify brain areas with altered rates of local cerebral glucose utilization (LCGU) in vivo in response to peripheral I-nicotine administration (0.1, 0.3, 1.0, and 1.75 mg/kg, s.c.). Nicotine stimulated LCGU primarily in areas reported to contain nicotine binding sites, indicating that the sites are true receptors. Increases in LCGU of 100% or more over control were obtained in the medial habenula, fasciculus retroflexus, superior colliculus, and median eminence. Substantial stimulation (50-100% increases) also was obtained in the cerebellar vermis, interpeduncular nucleus, and anteroventral and interanteromedial thalamic nuclei. Moderate increases (20-50%) were observed in the reticular nucleus of the medulla, paramedian lobule, nucleus of the spinal tract of the trigeminal nerve, presubiculum, subiculum, red nucleus, ventral tegmental area, substantia nigra, nucleus ambiguus, nucleus tractus solitarius, dorsal lateral geniculate nucleus, mammillothalamic tract, and fornix. The greatest stimulation in most affected areas was obtained with 0.3 mg/kg nicotine administered at 2 min, but not longer, before 14C-DG. Effects of nicotine on LCGU were antagonized by mecamylamine. The findings indicate that the interaction of nicotine with specific binding sites is coupled to cerebral energy metabolism. The distribution of in vivo cerebral metabolic effects of nicotine implicates various brain regions in the behavioral and physiological effects of nicotine.

Effects of nicotine on local cerebral glucose utilization in the rat

Effects of L-cocaine on local cerebral glucose utilization in the rat.

Pharmacological responses to the intracerebral administration of nicotine.

(R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane or a physiologically acceptable salt thereof is used for the manufacture of a medicament for the treatment of extrapyramidal movement disorders and/or adverse effects in extrapyramidal movement disorders. A preferred salt is (R)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane hydrochloride.

Novel use of (r)-(-)-2-[5-(4-fluorophenyl)-3-pyridylmethylaminomethyl]-chromane and its physiologically acceptable salts

Numerous investigations have been carried out to elucidate cholinergic mechanisms in the central nervous system (CNS). Bhattacharya and Feldberg (1958), using perfusion of cerebral ventricles in cat, found that acetylcholine (ACh) was released into the effluent. Ryall (1963) reported that ACh is contained within synaptic endings and Curtis, Ryall and Wilkins (1965) observed the presence of ACh, cholinacetylase and cholinesterase in the CNS. Dhawan, Gupta, Dixit and Chandra (1965) showed the presence of muscarinic receptors in the CNS of dogs.

K. S. Dixit

Papers

Effect of nicotine administration into the lateral cerebral ventricles of mice provides evidence for cholinergic mechanisms in the CNS