Exposure To A High-Fat Diet Decreases Sensitivity To Δ9-Tetrahydrocannabinol-Induced

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Exposure to a high-fat diet decreases sensitivity to Δ9-tetrahydrocannabinol-induced motor effects in female rats

Jenny L. Wiley Corresponding Author Contact Information, E-mail The Corresponding Author, Amanda R. Jones, M. Jerry Wright Jr.
Virginia Commonwealth University, Department of Pharmacology & Toxicology, Richmond, VA 23298-0613, USA

Received 24 May 2010; revised 7 September 2010; Accepted 9 September 2010. Available online 17 September 2010.

Arachidonic acid, a fatty acid component of neuronal cell membranes, forms the backbone of endogenous ligands of the endocannabinoid system. The lipid nature of this system may make it particularly susceptible to changes in fat content of the diet, which may, in turn, affect endocannabinoid tone and subsequent changes in receptor expression or activity. The latter would also be expected to affect responses to exogenous cannabinoids. The purpose of the present study was to determine the effects of a high-fat diet on sensitivity to the pharmacological effects of Δ9-tetrahydrocannabinol (Δ9-THC). Male and female Long-Evans rats were fed either a diet of standard rodent chow or chow enhanced with corn oil. Subsequently, they were repeatedly assessed for Δ9-THC-induced hypomobility, catalepsy and hypothermia. Female rats that received the high-fat diet beginning in adolescence or in adulthood became significantly less sensitive to the effects of Δ9-THC on motor behavior, but not its hypothermic effects, with faster development of decreased sensitivity in female rats that began the high-fat diet as adults. In contrast, diet-induced differences either did not occur, or were less pronounced, in male rats of both ages. After acute injection, brain and blood levels of Δ9-THC and its two primary metabolites were similar regardless of diet. Combined with the fact that diet differentially affected only some of the measures, these results suggest that pharmacokinetic differences cannot fully account for the effects of the high-fat diet on response to Δ9-THC. Further, these results suggest that dietary fat content may represent an important consideration in predicting the effects of marijuana in females.

Keywords: Cannabinoids; Females; High-fat diet; Marijuana abuse; Sex differences; Δ9-tetrahydrocannabinol

Source: Exposure to a high-fat diet decreases sensitivity to ?9-tetrahydrocannabinol-induced motor effects in female rats