REVERSIBLE EFFECTS OF ACUTE AND LONG-TERM ADMINISTRATION OF DELTA-9-TETRAHYDROCANNABINOL (THC) ON MEMORY IN THE RAT

A study was designed to develop a measure of both acute and chronic effects of THC administration on memory in the rat. Errors in an 8-arm radial maze, before and after two delay intervals (5 s and 1 h, introduced between the fourth and the fifth arm choice), constituted the principal dependent measures. The first experiment involved testing the animals shortly after administration of 1.25 mg/kg THC. The drug did not affect performance in the pre-delay tests, although a significant effect was observed after the 5-s delay but not after 1-h delay. In the second experiment, 5 mg/kg THC or saline were administered 6 days/week for 90 days. Testing was conducted 18 h after each drug administration. During chronic administration the pre-delay performance did not differ between groups but the post-delay performance of the THC group deteriorated in a gradual manner, relative to their controls, in both the 5-s and 1-h delay conditions. After discontinuation of drug administration, the differences between groups reversed only after 30 days. The results provided evidence that both acute and chronic administration of THC affected working-memory in the radial arm maze test, although it did not interfere with the general cues of the task (reference memory). Chronic drug effects on memory were reversible after prolonged abstinence. Thus, the 8-arm radial maze task proved to be a useful measure of THC effects on memory and could be further used to investigate more thoroughly the mechanisms involved in such drug effects. In addition, since hippocampal formation is involved in learning and memory processes, it was hypothesized that THC effects on memory could be mediated by a hippocampal dysfunction.