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Dose‐dependent effects of Δ 9 ‐tetrahydrocannabinol on rates of local cerebral glucose utilization in rat
Author(s) -
Freedland Cory S.,
Whitlow Christopher T.,
Miller Mack D.,
Porrino Linda J.
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10089
Subject(s) - delta 9 tetrahydrocannabinol , cannabinoid , chemistry , tetrahydrocannabinol , antagonist , delta , cannabinoid receptor , pharmacology , metabolism , rimonabant , medicine , endocrinology , receptor , biology , biochemistry , engineering , aerospace engineering
Recent reports have demonstrated that Δ 9 ‐tetrahydrocannabinol (Δ 9 ‐THC) stimulates locomotor activity at low doses (<2.5 mg/kg), while higher doses (>2.5 mg/kg) produce decreases in spontaneous activity. Using quantitative 2‐[ 14 C]deoxyglucose (2‐DG) autoradiography, we systematically studied the effects of acute Δ 9 ‐THC on rates of local cerebral glucose utilization. The first series of experiments was designed to determine if Δ 9 ‐THC‐mediated changes in cerebral metabolism followed a clear dose–response relationship. Adult male Sprague‐Dawley rats were treated with either vehicle or Δ 9 ‐THC (0.25–2.5 mg/kg) and the 2‐DG procedure was initiated 15 min following exposure. Administration of 2.5 mg/kg Δ 9 ‐THC produced significant decreases in cerebral metabolism in most brain regions studied. In contrast, administration of 0.25 mg/kg Δ 9 ‐THC produced no significant alterations in any brain region studied, while 1.0 mg/kg of Δ 9 ‐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 Δ 9 ‐THC‐induced changes in functional activity were measured. Pretreatment with SR141716A attenuated the majority of functional changes produced by Δ 9 ‐THC, suggesting that these effects are primarily mediated by central cannabinoid receptors. Moreover, these findings indicate that the effects of Δ 9 ‐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. © 2002 Wiley‐Liss, Inc.