Differential effects of the cannabinoid agonist WIN55,212-2 on delay and trace eyeblink conditioning

Central cannabinoid-1 receptors (CB1R) play a role in the acquisition of delay eyeblink conditioning (EBC) but not trace EBC in humans and animals. However, it is not clear why trace conditioning is immune to the effects of cannabinoid receptor compounds. The current study examined the effects of variants of delay and trace conditioning procedures to elucidate the factors that determine the effects of CB1R agonists on EBC. In Experiment 1, rats were administered the cannabinoid agonist WIN55,212-2 during delay, long-delay, or trace conditioning. Rats were impaired during delay and long-delay, but not trace conditioning; the impairment was greater for long-delay than delay conditioning. Trace conditioning was further examined in Experiment 2 by manipulating the trace interval and keeping constant the conditioned stimulus (conditional stimulus [CS]) duration. It was found that when the trace interval was 300 ms or less, WIN55,212-2 administration impaired the rate of learning. Experiment 3 tested whether the trace interval duration or the relative durations of the CS and trace interval were critical parameters influencing the effects of WIN55,212-2 on EBC. Rats were not impaired with a 100-ms CS, 200-ms trace paradigm but were impaired with a 1,000-ms CS, 500-ms trace paradigm, indicating that the duration of the trace interval does not matter, but the proportion of the interstimulus interval occupied by the CS relative to the trace period is critical. Taken together, the results indicate that cannabinoid agonists affect cerebellar learning when the CS is longer than the trace interval.