Pharmacology Biochemistry & Behavior, Vol. 3, pp. 583--588. Copyright © 1975 by ANKHO International Inc. All rights of reproduction in any form reserved. Printed in the U.S.A. Glucoprivic (2DG) Eating in Rats Despite Knife Cut Induced Hyperphagia I KATHERINE A. HOUFI" Department of Physiology, Biochemistry and Pharmacology, New York State Veterinary College Cornell University, Ithaca, NY 14853 AND RICHARD M. GOLD Department of Psychology, University of Massachusetts-Amherst, Amherst, MA 01002 (Received 22 August 1974) HOUPT, K. A. AND R. M. GOLD. Glucoprivic (2DG) eating in rats despite knife cut induced hypothalamic hyper- phagia. PHARMAC. BIOCHEM. BEHAV. 3(4) 583-588, 1975. - Two weeks after parasagittal hypothalamic knife cuts, baseline eating was elevated and 300 mg/kg 2 deoxy-D-glucose (2DG) did not further stimulate food intake. Five weeks postoperatively the food intake baseline had fallen and an eating response to 300 mg/kg 2DG was now seen (/9<0.005). In this delayed (static) phase intake was also stimulated by 150 mg/kg 2DG (p<0.005). 600 mg/kg did not stimulate intake in the lesioned rats at any time, although sham-operated rats always responded positively to this high dose. In conclusion, the neural substrate damaged in hypothalamic hyperphagic rats does not appear to mediate eating in re- sponse to glucoprivation. The eating response is masked by high baseline intake in the dynamic phase, but reappears in the static phase. Glucoprivation Parasagittal knife cuts Hypothalamic hyperphagia Obesity 2-Deoxyglucose IN intact rats glucoprivation produces an increase in food intake. Glucoprivation can be produced by the adminis- tration of 2-deoxy-D-glucose (2DG) which inhibits glucose utilization within the cell [5]. Systemic 2DG stimulates food intake [26]. Intraventricular [19] and intracranial 2DG [3] also stimulate food intake. A second way fre- quently used to produce glucoprivation is by the adminis- tration of insulin. Insulin has also been shown to stimulate food intake [ 18,28]. Rats which have recovered from the aphagia that follows lateral hypothalamic brain lesions eat neither in response to 2DG [29] nor in response to insulin [28 ]. This suggests that lateral hypothalamic cells or fibers of passage are involved in responding to a decrease in metabolizable glucose. Selec- tive depletion of brain dopamine by intraventricular 6-hydroxydopamine [27] or medial forebrain bundle lesions [4] also prevent the response to 2DG. This supports the fiber of passage interpretation because the nigrostriatal dopamine bundle passes through the lateral hypothalamus [2,10]. It has been suggested that the medial hypothalamus may also play a rote in the glucoprivic eating response, but the data supporting this suggestion are inconsistent. On the one hand, rats obese as a result of medial hypothalamic lesions increase their short term food intake following insulin [28], intraventricular 2DG [20], or intravenous 2DG [23]. Mfiller et el. [22], on the other hand, report that rats with medial hypothalamic lesions do not eat in response to systemic 2DG. In the present study we report that 2DG produces a robust eating response in hyperphagic obese rats. Furthermore, we demonstrate how the particu- lar experimental conditions used by Mfiller et al. [22] could easily explain failure to obtain a reliable eating response. The apparent contradiction may be due to differ- ences in the size or location of the medial hypothalamic lesions in the various studies. Also, rats with particularly effective lesions may have such a high base rate of food intake, especially in the rapid weight gain or dynamic phase, that eating in response to 2DG is masked. Finally, high doses of 2DG computed on a per kg of rat basis may be an overdose for obese rats. 1Supported by USPHS Special Fellowship 5F03 AM55321-02 to K. A. H., and USPHS Grant MH-13561 to R. M. G. Request for reprints should be sent to Dr. Katherine Houpt, Department of Physiology, N. Y. S. Veterinary College, Cornell University, Ithaca, NY 14850. 583