Metabolic mapping of the time-dependent effects of delta 9-tetrahydrocannabinol administration in the rat.

Abstract

Delta(9)-Tetrahydrocannabinol (THC) has a long duration of action. Studies have shown that effects on some behavioral endpoints can persist for as long as 24 h after exposure, but the neural substrates underlying these long-lasting effects have not yet been determined. The purpose of the present study was to identify the neuroanatomical substrates associated with the temporal course of the effects of the acute administration of moderate to high doses of THC using the quantitative autoradiographic 2-[(14)C]deoxyglucose (2DG) method. Male Sprague-Dawley rats ( n=4-5 per group) were administered THC (0.0, 2.5 or 10 mg/kg, intraperitoneally), and the 2DG procedure was initiated 15 min, 6 h, or 24 h after treatment. To establish the behavioral profile of THC administration, locomotor activity and core body temperature were measured at corresponding time points. The administration of THC produced widespread dose-dependent reductions in rates of cerebral metabolism when the 2DG method was applied 15 min after treatment. A more limited set of structures was affected when the 2DG method was applied 6 h after THC administration, closely paralleling the effects of THC on locomotor activity and core body temperature. However, 24 h after administration, glucose utilization remained depressed within mesolimbic and amygdalar regions. These data demonstrate that the functional consequences of acute administration of THC follow a distinct temporal course that is regionally specific. That functional activity remains depressed in areas involved in the processing of motivational and emotional information suggests that behaviors subserved by these structures (e.g. anxiety, stress, and reward) may remain altered for as long as 24 h after a single exposure to THC.