Adolescent exposure of JWH-018 "Spice" produces subtle effects on learning and memory performance in adulthood (2012)

The active components associated with the bio-designer drugs known variously as "Spice" or "K2" have rapidly gained in popularity among recreational users, forcing the United States Drug Enforcement Administration to classify these compounds as Schedule I drugs in the Spring of 2011. However, although there is some information about many of the synthetic cannabinoids used in Spice products, little is known about the consequences of the main constituent, (1-pentyl-3-(1-naphthoyl)indole; JWH-018), on neuropsychological development or behavior. In the present experiment, adolescent rats were given repeated injections of either saline or 100 µg/kg of JWH-018. Once the animals were 75 days of age, they were trained using tasks with spatial components of various levels of difficulty and a spatial learning set task. On early trials with water maze tasks of varying difficulty, the JWH-018 treated rats were impaired relative to controls. However, by the end of each phase of testing, drug and control animals were comparable, although on probe trials the drug-treated animals spent significantly less time in the target quadrant. In addition, the performance of the drug-treated rats was inferior to that of the control animals on a learning set task, suggesting some difficulty in adapting their responses to changing task demands. The results suggest that chronic exposure to this potent cannabinoid CB1 receptor agonist during adolescence is capable of producing a variety of subtle changes affecting spatial learning and memory performance in adulthood, well after the drug exposure period.