Recent evidence suggests that sustained consumption of a high-fat diet is associated with reduced CB1 receptor expression in some brain areas. Many of the neuromodulatory functions of endogenous cannabinoids are mediated by the CB1 receptor. The CB1 receptor also mediates the behavioral and physiological effects of delta-9-tetrahydrocannabinol (delta-9-THC), the primary psychoactive constituent of marijuana. While high-fat diets are associated with region-specific changes in CB1 receptor expression, it is not clear whether such changes are behaviorally relevant. To that end, separate groups of male and female rats were placed on either a high-fat diet or a standard diet. Cannabinoid function was determined in a triad of measures (e.g., hypothermia, gross locomotion, time on bar apparatus) at postnatal day 30 (PD30), PD44, PD68 and PD114. These age points respectively correspond to rodent models of early adolescence, late adolescence, early adulthood and full maturity in humans. Male rats were also tested at PD37 and PD61. Subsequently, the antinociceptive properties of delta-9-THC and the effect of delta-9-THC on food intake were also measured. After 38 days, female rats maintained on a high-fat diet were significantly less sensitive to the psychomotor effects of delta-9-THC than were the female rats maintained on the control diet. These diet-related differences persisted into full maturity. Female rats maintained on a high-fat diet were also less sensitive to changes in food intake caused by delta-9-THC than were female rats maintained on the control diet. In contrast, the hypothermic effects of delta-9-THC were not differentially affected by the type of diet consumed. Likewise, female rats maintained on a high-fat diet exhibited tail-flick latencies that were indistinguishable from those of female rats maintained on the control diet. With two minor exceptions, and in sharp contrast to female rats, sensitivity to the pharmacological effects of delta-9-THC was not differentially affected by the type of diet in male rats. In short, female rats maintained on a high-fat diet appeared to be cross-tolerant to the psychomotor and hyperphagic effects of delta-9-THC while male rats maintained on a high-fat diet exhibited responses to delta-9-THC that were virtually indistinguishable from control animals.
| Identifer | oai:union.ndltd.org:vcu.edu/oai:scholarscompass.vcu.edu:etd-2767 |
| Date | 05 May 2009 |
| Creators | Wright, Mayo |
| Publisher | VCU Scholars Compass |
| Source Sets | Virginia Commonwealth University |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | Theses and Dissertations |
| Rights | © The Author |
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