The effect of D-amphetamine on energy balance in hypothalamic obese rats

G. C. Kennedy, J. Mitra
1963 British Journal of Nutrition  
A number of stimulants of the central nervous system are used to treat obesity because they are believed to inhibit appetite. The anorexic effect is difficult to demonstrate unequivocally in man; Wilson & Schild (1959), for example, say of D-amphetamine, the best-known drug of this group, that its chief value is to make it less unpleasant for the co-operative patient to deny himself food. Nevertheless, it is well established that amphetamine can cause weight losses in both man and animals
more » ... n and animals (Harris, Ivy & Searle, 1947; Williams, Daughaday, Rogers, Asper & Beverly, 1948; Adlersberg & Mayer, 1949) . The possibility exists that the stimulant effect of the drugs may contribute to such weight loss, for spontaneous locomotor activity is an important factor in determining energy balance (Mayer, 1955) and is regulated to a great extent by the same hypothalamic region that governs appetite (Kennedy, 1961 ; Kennedy & Mitra, 1963) . The object of the work described in this paper was to find out how lesions in the hypothalamus of rats affected both the stimulant and the anorexic action of amphetamine. EXPERIMENTAL We used thirty-five young female rats of the Lister hooded strain, ten normal and twenty-five made hyperphagic by placing bilateral electrolytic lesions in the lateral part of the ventromedial nuclei of the hypothalamus. All the control animals and seven of the operated ones were housed in activity-measuring cages of the treadmill variety; the remainder of the operated rats were kept in ordinary cages. The techniques of operation and activity measurement have been fully described (Kennedy & Mitra, 1963) . The experiments took place in an air-conditioned room between 75 and 80" F with lighting from 6 a.m. to 6 p.m. The diet was the powdered MRC diet 41 B (Bruce, 1958), of which a weighed amount was given daily, moistened with an equal weight of water, any rejected food being dried before reweighing. D-amphetamine sulphate was given when appropriate, mixed with the diet in the proportion of 0.0625 mg/g dry diet. With an approximate daily intake of 15-20 g, a normal female rat weighing 250 g thus received 4-5 mg/kg body-weight daily. After hypothalamic operation all rats were given normal food ad lib. for at least 5 days and their hyperphagia was graded as 'severe' if they ate more than 40 g/day and as 'moderate' if they ate less (Fig. I) . Their intake was then restricted until they regained their pre-operative weight, after which sufficient food was given to maintain weight gain at the slow rate seen before operation; the amount varied from day to day and from animal to animal and was found by trial and error. The effects of amphetamine at https://doi.
doi:10.1079/bjn19630059 pmid:14083955 fatcat:53d22urpqbbz5bd43n6jmrfzs4