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The Role of Hypothalamic Insulin and Dopamine in the Anorectic Effect of Cocaine and d-amphetamine

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Technical Report

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Uniformed Services University Of The Health Sciences Bethesda United States

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Cocaine and amphetamines are among the most reinforcing of all psychoactive drugs. Although evidence of the dangers of the use of these drugs is increasing, the number of people who consume these drugs continues to grow. Many of the actions of cocaine and amphetamines seem to be the result of stimulation and potentiation of several amines in the CNS. However, the effects of these drugs on neurochemical systems have not been fully established. Likewise, the neurochemical mechanisms mediating the behavioral effects of these drugs are not clear. One of the best established behavioral effects of cocaine and amphetamines is the suppression of appetite. However, the mechanisms mediating this effect are unknown. The present experiments examined the effect of repeated administration of cocaine HCl or d-amphetamine sulfate on hypothalamic insulin, norepinephrine, and dopamine, plasma insulin, and pancreatic insulin and examined the relationship of these effects to food consumption and body weight changes in an attempt to shed some light on the mechanisms mediating the anorectic effect of these drugs. In Experiment 1, male rats were administered cocaine HCl via Alzet miniosmotic pumps, for six days. The animals were assigned to one of five groups 70 mgkgday of cocaine HCl, 50 mgkgday of cocaine HCl, 70 mgkgday of cocaine HCl 0.5 Uday of purified pork insulin, 0.5 Uday of purified pork insulin, or physiological saline. In Experiment 2 animals were administered d-amphetamine sulfate via Alzet miniosmotic pumps for two days. The animals were assigned to one of four groups 50 mgkgday of d-amphetamine sulfate, 25 mgkgday of d-amphetamine sulfate, 50 mgkgday of d-amphetamine sulfate 0.5 Uday of purified pork insulin, or physiological saline. Cocaine HCI and d-amphetamine sulfate administration reduced food consumption.

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