Dose‐dependent effects of Δ9‐tetrahydrocannabinol on rates of local cerebral glucose utilization in rat

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Abstract
Recent reports have demonstrated that Δ9-tetrahydrocannabinol (Δ9-THC) stimulates locomotor activity at low doses (2.5 mg/kg) produce decreases in spontaneous activity. Using quantitative 2-[14C]deoxyglucose (2-DG) autoradiography, we systematically studied the effects of acute Δ9-THC on rates of local cerebral glucose utilization. The first series of experiments was designed to determine if Δ9-THC-mediated changes in cerebral metabolism followed a clear dose–response relationship. Adult male Sprague-Dawley rats were treated with either vehicle or Δ9-THC (0.25–2.5 mg/kg) and the 2-DG procedure was initiated 15 min following exposure. Administration of 2.5 mg/kg Δ9-THC produced significant decreases in cerebral metabolism in most brain regions studied. In contrast, administration of 0.25 mg/kg Δ9-THC produced no significant alterations in any brain region studied, while 1.0 mg/kg of Δ9-THC produced a restricted pattern of metabolic decreases. Significant decreases in metabolism following 1.0 mg/kg were concentrated in structures subserving limbic and sensory functions. In a second series of experiments, the effects of pretreatment with the cannabinoid receptor antagonist SR141716A (1.0 mg/kg) on Δ9-THC-induced changes in functional activity were measured. Pretreatment with SR141716A attenuated the majority of functional changes produced by Δ9-THC, suggesting that these effects are primarily mediated by central cannabinoid receptors. Moreover, these findings indicate that the effects of Δ9-THC on cerebral metabolism are dose-dependent and that there are regional differences in the metabolic response to acute cannabinoid exposure. Synapse 45:134–142, 2002.