Addictive agents and intracranial stimulation: Daily amphetamine and hypothalamic self-stimulation

Abstract

Twelve rats fixed with chronically indwelling electrodes for stimulation of the lateral hypothalamus were used to test for the effects of daily doses of amphetamine (2 and 4 mg/kg daily for 20 days). The rats' rate of pressing for brain stimulation was observed I, 4, and 23 h after injections in 5-min sessions. These doses did not reliably increase self-stimulation rates during the times of testing. During the 5 days following termination of injections, pressing rates of rats receiving amphetamine were slightly less than those of rats receiving a placebo.Amphetamine, at certain doses and regimens of testing, can accelerate pressing for lateral hypothalamic medial forebrain bundle (MFB) stimulation (Stein, 1964). Chronic use of amphetamine presumably produces something approaching psychoses in certain individuals (Bell, 1965; Ellinwood, 1968). Stein and Wise (1971) have suggested that affective psychoses are related to changes in levels of functional norepinephrine of the MFB system. Furthermore, amphetamine is known to increase available norepinephrine of the MFB (Stein & Wise, 1969, 1971. Despite the potentially important relationships among the actions of chronic dosing with amphetamine, adrenergic functions, and the MFB, there have been only limited tests of daily amphetamine and MFB self-stimulation. Consequently, it was decided, while testing the effects of daily injections of morphine on self-stimulation (Bush, Bush, Miller, & Reid, 1976), to test concurrently for the effects of daily injections of amphetamine.These tests with amphetamine are limited. Only two doses, 2 and 4 mg/kg, were used. These doses were · selected because larger doses, when given daily, produce serious debility (West, Hunsicker, Propheter, Taylor, & Reid, 1972). The self-stimulation tests were confmed to sessions 1, 4, and 23 h after injections across 20 days and to days immediately before and after days of injections. Because of the limitations of the procedure, this study is only a preliminary study of the effects of chronic dosing of amphetamine on self-stimulation; results suggest that more systematic investigation might be interesting. METHOD SubjectsThe subjects were 12 adult male Sprague-Dawley rats. Each was fIxed, using standard procedures, with a chronically Work was supported by a grant from Bradley University's Board for Research and Grant DAOI049 from the National Institute of Drug Abuse, DHEW. indwelling bipolar electrode. The stainless steel electrodes (Plastic Products ms 303) were insulated except at the cross section of the stimulating tips. The tips were separated from each other only by the width of the insulation.The sites of intracranial stimulation (ICS) were verified by direct inspection of frozen sections of the subjects' brains and by inspection of photographs of enlarged images of those sections (Guzman, Flores, Alcarez, & Fernandez, 1968). Electrode tips were within the lateral hypothalamus and the primary structure of ICS was the MFB. ApparatusThe experimental chamber was a Plexiglas box (30 x 25 x 43 cm...

Addictive agents and intracranial stimulation:Daily amphetamine and hypothalamic self-stimulation

“…With rats pressing daily for hypothalamic intracranial stimulation (ICS), Miller, Bush, and Reid (1976) tested for the effects of 20 days of administration of 2-and 4-mg/kg doses of d-amphetamine with testing at 1, 4, and 23 h after injections. Under this regimen, doses hardly modified pressing rates.…”