Differential Effects of Delta9-THC on Learning in Adolescent and Adult rats

1. Differential Effects of Delta9-THC on Learning in Adolescent and Adult rats Young May Cha, Aaron M. White , Cynthia M. Kuhn , Wilkie A. Wilson,H.S. Swartzwelder Pharmacology, Biochemistry and Behavior 83 (2006) pgs. 448–455

2. Introduction • Studied the effects of delta9-tetrahydrocannabinol (THC) in both adolescent and adult rats. • THC is the main psychoactive substance found in the Cannabis plant • Used high and low doses of THC

3. Hypothesis • They hypothesized that THC would impair learning more potently in male adolescent animals compared to male adults.

4. Methods • 96 male adolescent rats & 96 male adult rats • Injected with either a high dose or low dose of THC • High Dose: 10.0 mg/kg • Low Dose: 2.5 mg/kg • Used the Morris water maze (MWM) as a tool to measure learning.

5. MethodsAcute • Experiment 1 • Assess the acute effects of THC on spatial learning. • Adolescent and adult rats received injections of THC (5mg/kg) or the control vehicle solution. • Thirty minutes after the injection, animals began training on the spatial task in the MWM. • Experiment 2 • Assess the effects of a lower dose and a higher dose on spatial and non-spatial learning in the MWM. • Low dose-2.5mg/kg • High dose-10mg/kg.

6. MethodsChronic • Experiment 3-Assessed the long-lasting effects of chronic THC treatment on spatial learning. • Adolescent and adult rats were given injections of a control solution or a THC solution (5.0mg/kg) once daily for 21 days. • Twenty-eight days after the last injection, the rats were trained, drug-free, on the spatial task in the MWM. • 48 hours after the completion of the spatial task, the same rats were also trained on the non-spatial version of the water maze task.

7. ResultsAcute-Experiment 1 • Although the performance of adolescent rats treated with THC improved, they never reached the level of performance of the controls (Fig. 1a). • There was no significant effect of THC on adults in spatial learning • (Fig. 1b).

8. ResultsAcute-Experiment 2

9. ResultsAcute • Spatial Learning • Overall, THC impaired spatial learning across the five day testing period. • THC also impaired learning more in adolescent rats than in adult rats at both the low and high doses. • Non-Spatial Learning • THC also impaired non-spatial learning across the five-day testing period. • At both doses, THC impaired non-spatial learning more powerfully in adolescent rats

10. ResultsChronic • There were no overall effects of chronic pre-exposure to THC during either adolescence or adulthood, in both the spatial or non-spatial task.

11. Conclusion • Acute treatment with THC inhibited both spatial and non-spatial learning in the water maze more powerfully in male adolescent rats than in male adults. • Chronic THC treatment, either during adolescence or adulthood, had no effect on subsequent learning four weeks after the last exposure to THC. • More research will be needed to determine which periods of development, and which cognitive and behavioral functions are most susceptible to the effects of THC.

12. Questions?