Effects of combined use of alcohol and delta-9-tetrahydrocannibinol on working memory in Long Evans rats.

The increase in social acceptance and legalization of cannabis over the last several years is likely to increase the prevalence of its co-use with alcohol. In spite of this, the potential for effects unique to co-use of these drugs, especially in moderate doses, has been studied relatively infrequently. We addressed this in the current study using a laboratory rat model of voluntary drug intake. Periadolescent male and female Long-Evans rats were allowed to orally self-administer ethanol, Δ9-tetrahydrocannibinol (THC), both drugs, or their vehicle controls from postnatal day (P) 30 to P47. They were subsequently trained and tested on an instrumental behavior task that assesses attention, working memory and behavioral flexibility. Similar to previous work, consumption of THC reduced both ethanol and saccharin intake in both sexes. Blood samples taken 14 h following the final self-administration session revealed that females had higher levels of the THC metabolite THC-COOH. There were modest effects of THC on our delayed matching to position (DMTP) task, with females exhibiting reduced performance compared to their control group or male, drug using counterparts. However, there were no significant effects of co-use of ethanol or THC on DMTP performance, and drug effects were also not apparent in the reversal learning phase of the task when non-matching to position was required as the correct response. These findings are consistent with other published studies in rodent models showing that use of these drugs in low to moderate doses does not significantly impact memory or behavioral flexibility following a protracted abstinence period.

Effects of combined use of alcohol and delta-9-tetrahydrocannibinol on working memory in Long Evans rats.

The increase in social acceptance and legalization of cannabis over the last several years is likely to increase the prevalence of its co-use with alcohol. In spite of this, the potential for effects unique to co-use of these drugs, especially in moderate doses, has been studied relatively infrequently. We addressed this in the current study using a laboratory rat model of voluntary drug intake. Periadolescent male and female Long-Evans rats were allowed to orally self-administer ethanol, Î" 9 -tetrahydrocannibinol (THC), both drugs, or their vehicle controls from postnatal day (P) 30 to P47. They were subsequently trained and tested on an instrumental behavior task that assesses attention, working memory and behavioral flexibility. Similar to previous work, consumption of THC reduced both ethanol and saccharin intake in both sexes. Blood samples taken 14h following the final self-administration session revealed that females had higher levels of the THC metabolite THC-COOH. There were modest effects of THC on our delayed matching to position (DMTP) task, with females exhibiting reduced performance compared to their control group or male, drug using counterparts. However, there were no significant effects of co-use of ethanol or THC on DMTP performance, and drug effects were also not apparent in the reversal learning phase of the task when non-matching to position was required as the correct response. These findings are consistent with other published studies in rodent models showing that use of these drugs in low to moderate doses does not significantly impact memory or behavioral flexibility following a protracted abstinence period.

Wheel running leads to sex-specific effects on Western diet-associated glucose homeostasis and brain insulin signaling without altering food-related impulsive choice.

OBJECTIVES: There is a clear association between obesity and impulsivity. While exercise can suppress weight gain and decrease impulsive choice (IC), the relationship between impulsivity, the consumption of palatable, energy dense diets, and exercise is unclear. We examined IC before and after Western diet (WD) exposure in rats of both sexes and whether exercise would rescue any diet-mediated increases in IC. Our hypotheses were twofold: first, increased impulsivity would be associated with higher WD preference in a positive feedback loop and second, increased WD consumption would impair both peripheral and central insulin signaling, both of which exercise would attenuate. METHODS: Following baseline assessment of IC through a delay discounting task, rats were divided into naïve, sedentary (Sed), or wheel running (WR) groups for a 5-week WR and two-diet choice period after which rats underwent an oral glucose (OGTT) and insulin tolerance test (ITT) in addition to a re-test of IC. Insulin induced Akt-GSK3ß signaling in the brain was examined using western blot. RESULTS: All Sed rats preferred the WD diet, and all WR rats initially avoided the WD but subsequently reversed their avoidance to preference with females reversing earlier than males. Exercise suppressed weight gain and adiposity to a greater extent in males than females. Only WR males showed improved glucose clearance during OGTT, but both male and female WR rats had a faster recovery of hypoglycemia during ITT. Furthermore, WR rescued WD-induced deficits in hypothalamic Akt-GSK3ß signaling in males but not females. In the prefrontal cortex, however, WD and WR both reduced Akt-GSK3ß signaling in males but not females. There were no sex differences in IC at baseline, and all rats made more impulsive choices during the re-test independent of diet, sex, or exercise. DISCUSSION: The results suggest that while exercise may have a greater efficacy at attenuating diet-mediated metabolic dysregulation in males, it has some beneficial effects for females and highlights the need to develop sex-specific interventions for restoring energy balance.