Ethanol and Cocaine Interactive Effects on Local Cerebral Glucose Utilization (LCGU)
Abstract
The present study examined the differences in local cerebral glucose utilization (LCGU) following cocaine and ethanol, alone and in combination. LCGU is a measure of neuronal activation of specific areas in the brain. Cocaine and ethanol have both been shown to activate many brain areas, some of which overlap, such as the mesocorticolimbic dopamine pathway (i.e., the postulated reward pathway). Therefore, it was hypothesized that the combination, cocaine and ethanol, would cause additive activation in these areas. Cocaine (5 mg/kg, intravenously (IV)) or ethanol (1 or 3 g/kg, intraperitoneally (IP)) were administered alone or in combination to five separate groups of male, Sprague-Dawley rats. A sixth group served as a control group with saline vehicle administered in lieu of the two drugs. Following drug administration, [14C]2-deoxyglucose (2-[14C] DG) was injected IV, and rats were killed after 45 minutes. Brains were removed, processed and analyzed for LCGU. Cocaine treatment yielded no significant main or interactive effects in any brain region measured. The ethanol (1 g/kg) alone group was significantly increased beyond the high dose alone in specific regions, such as the caudate and mesocorticolimbic pathway. There were significant differences between the two groups given combination treatments, wherein the ethanol (1 g/kg)/cocaine group had potentiated levels of LCGU in the nucleus accumbens, caudate, mammillary bodies, thalamus and median raphe above that of high dose ethanol/cocaine. Overall, the lower dose of ethanol, regardless of cocaine treatment, increased levels of LCGU across most of the regions evaluated; in contrast, the higher dose of ethanol, regardless of cocaine treatment, did not increase LCGU. The results confirm the low-dose ethanol stimulatory effect on LCGU, whereas higher doses of ethanol were depressed relative to the low dose group, but comparable to saline controls. This effect remained true for ethanol co-administered with cocaine. The central hypothesis of an additive effect of cocaine and ethanol on LCGU was not supported. (Supported in part by DA09362 and AA07462).
Degree
Ph.D.
Advisors
Neal-Beliveau, Purdue University.
Subject Area
Neurosciences|Psychobiology|Physiological psychology
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