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Degree Name

Doctor of Philosophy




Destruction of either the ventromedial hypothalamus (VMH) or the dorsolateral tegmentum (DLT) in rats induces hyperphagia and consequent obesity, but only DLT destruction diminishes the anorexic properties of amphetamine. These findings suggest that the DLT, but not the VMH, is the neural substrate for amphetamine anorexia. The present experiments reexamine the mediation of amphetamine anorexia by putative satiety mechanisms in either the VMH or the DLT and control a number of procedural problems evident in earlier work such as body weight level during drug testing;In Experiments 1-3, the anorexic properties of amphetamine (0.5, 1.0, and 2.0 mg/kg) and phenylpropanolamine (5.0, 10.0, and 20.0 mg/kg) were assessed in 23-hour fasted female control, VMH, and DLT rats while the rats were maintained at 80% of their preoperative body weight levels. When the rats were offered a palatable high-fat test diet (Experiment 1), control rats displayed variable anorexia to amphetamine while both VMH and DLT rats exhibited attenuated amphetamine anorexia. When fed a pellet test diet (Experiment 2), however, both control and VMH rats displayed dose-dependent amphetamine anorexia while only DLT rats displayed attenuated anorexia. The outcomes of Experiments 1 and 2 indicate that diet palatability is an important determinant of drug-induced anorexia and confirm earlier demonstrations that DLT destruction attenuates amphetamine anorexia. In Experiment 3, the generality of the attenuation of anorexia in DLT rats was examined using phenylpropanolamine (PPA), an anorexic substance that does not have marked arousal properties. When fed a pellet test diet, DLT rats displayed anorexia to PPA that was indistinguishable from that observed in both control and VMH rats;The demonstration that DLT rats displayed attenuated anorexia to amphetamine, but not to PPA, suggested that DLT lesions may attenuate amphetamine anorexia indirectly by blocking that portion of amphetamine anorexia that results from incompatible arousal behaviors. Such an interpretation, however, was not supported by the findings of Experiment 4, in which amphetamine (2.0 mg/kg) induced comparable hyperactivity in control, VMH, and DLT rats;Finally, amphetamine, in conjunction with a high ambient temperature, induces hyperthermia and general malaise as indexed by the observation that amphetamine will support a conditioned taste aversion. These findings suggest that malaise associated with hyperthermia may partially contribute to the anorexia induced by amphetamine. Experiment 5 demonstrated that amphetamine (2.0 mg/kg) induced significant hyperthermia (rectal) in control and VMH rats, but was without significant effect on rectal temperature in DLT rats;The present findings seriously question the notion that a satiety mechanism within the DLT mediates the anorexia induced by amphetamine. The present data instead suggest that rats with DLT destruction continue to feed following amphetamine treatment because amphetamine does not induce hyperthermia in these animals.



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Paul Jeff Wellman



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132 pages