Caffeine restores feeding response to 2-deoxy-D-glucose in 6-hydroxydopamine-treated rats.
A large portion of the central catecholaminergic nerve terminals of the rat are destroyed by administering 6-hydroxydopamine (6-HDA) via the cerebrospinal fluid. Animals lesioned in this way often appear normal, yet show many subtle behavioural abnormalities. We have been examining one example of this phenomenon, the failure of 6-HDA-lesioned rats to increase food intake when given a systemic injection of 2-deoxy-D-glucose (2-DG) (refs 5, 6). This glucose analogue seems to elicit feeding in intact rats due to its inhibition of glycolysis in cerebral chemoreceptor cells. We have proposed that lesioned animals do not eat because of an insufficient central catecholaminergic response to the severe decrease in glucose utilisation induced by 2-DG (ref. 10). If so, then pretreatments which serve to augment this neurochemical response might be expected to reinstate behavioural function. Consistent with this hypothesis, very large increases in telencephalic tyrosine hydroxylase activity in 6-HDA-lesioned animals, which occur following chronic insulin treatment, are associated with the restoration of 2-DG-induced feeding. Many of the physiological effects of catecholamines in the sympathetic nervous system seem to be mediated by an increase in the cyclic AMP concentration of the target cells. Methylxanthenes, such as caffeine and theophylline, inhibit phosphodiesterase, prevent cyclic AMP degradation, and thereby potentiate the catecholamine-stimulated rise in cyclic nucleotide. They also enhance many of the behavioural and physiological effects of catecholamines, presumably by the same mechanism. We therefore sought to determine whether the acute administration of those sympathomimetic agents, in intact and 6-HDA-lesioned rats, also would potentiate 2-DG-induced feeding, a behaviour that seems to be mediated, in part, by central catecholaminergic neurons. We report that caffeine restores the 2-DG-induced feeding response.[1]References
- Caffeine restores feeding response to 2-deoxy-D-glucose in 6-hydroxydopamine-treated rats. Stricker, E.M., Zimmerman, M.B., Friedman, M.I., Zigmond, M.J. Nature (1977) [Pubmed]
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