Acute and long-term effects of Δ9-tetrahydrocannabinol on object recognition and anxiety-like activity are age- and strain-dependent in mice

Use of exogenous cannabinoids disrupts the fine-tuned endocannabinoid receptor system, possibly leading to alterations in cognition, memory, and emotional processes that endure long after cannabinoid use has stopped. Long-term adolescent use may uniquely disrupt these behaviors when compared to adult use. The current study explored the acute and long-term behavioral effects of six 10mg/kg Δ9-tetrahydrocannabinol (THC) injections across the adolescent or early adult period in male inbred C57Bl/6J and DBA/2J mice. The acute and prolonged effects of THC on object memory using the novel object recognition task, unconditioned anxiety in the elevated plus maze and open field, and sedative effects in the open field were examined. Acute THC treatment resulted in anxiogenic activity in both strains, but only caused sedation in B6 mice. Repeated THC treatment resulted in a protracted effect on object recognition, but not unconditioned anxiety, assessed 4weeks later. In both strains, an adolescent history of THC treatment disrupted later object recognition. Interestingly, in B6 mice an adult history of THC exposure appeared to rescue a deficit in object recognition observed in vehicle-treated adults. Repeated THC administration also produced a protracted effected on CB1R protein expression. Animals treated with THC in adolescence maintained increased levels of CB1R protein expression compared to their adult THC-treated counterparts at five weeks following the last injection. These results indicate that THC use may have long-lasting effects with adolescence being a unique period of susceptibility

ACUTE FUNCTIONAL TOLERANCE TO ETHANOL IN MICE SELECTIVELY BRED FOR HIGH AND LOW ALCOHOL PREFERENCE DRINKING

poster abstractPropensity to develop acute functional (or within session) tolerance to alcohol (ethanol) may influence the amount of alcohol consumed, with higher drinking associated with greater acute functional tolerance (AFT). The goal of the current study was to assess this potential corre-lated response in second and third replicate lines of mice selectively bred for high (HAP2&3) and low (LAP2&3) alcohol preference drinking. We predicted that HAP mice would develop greater AFT to alcohol’s ataxic actions than LAP mice. Male and female HAP2&3 and LAP2&3 mice were tested for development of AFT on a static dowel task. This task requires that animals maintain balance on a wooden dowel in or-der to prevent falling. On test day, each mouse received one (1.75g/kg; experiment 1) or two (1.75g/kg and 2.0g/kg; experiment 2) injections of ethanol; an initial administration before being placed on the dowel and in another experiment, an additional administration after the first regain of balance on the dowel. Blood samples were tak-en immediately after loss of balance and regain in Experiment, 1 and after first and second regain in Experiment 2. It was found that HAP mice fell from the dowel significantly earlier and at lower BACs than LAP mice following the initial injection of ethanol and were therefore more sensitive. Furthermore, the single-injection experiment detected significantly greater AFT development (BAC2-BAC1) in HAP mice as compared to LAP mice, supporting our hypothesis. This study illus-trates the rapidity with which adaptive pharmacodynamic processes can take place which may contribute to excessive alcohol consumption