The synthetic cannabinoid WIN 55212-2 differentially modulates thigmotaxis but not spatial learning in adolescent and adult animals

Unlike Δ9-THC, the synthetic compound WIN 55212-2 (WIN) is a full agonist of endogenous cannabinoid receptors. Previous work has shown Δ9-THC to affect adolescent and adult animals differently on numerous behavioral measures of spatial memory, anxiety, and locomotor activity. However, far less is known about the developmental and neurobehavioral effects of WIN. To address this, we assessed the effect of WIN (1 mg/kg) on spatial learning in adolescent and adult rats using the Morris water maze. While all animals demonstrated decreased swim distance across days, WIN affected adolescents and adults differently. It improved performance in adolescents and resulted in a nearly significant performance decrement in adults. However, these effects were significantly related to thigmotaxis, which declined across days in the water maze testing protocol. WIN reduced thigmotaxis on days 1 and 2 (but not days 3-5) only in adolescents. The effect of age, treatment, and the age × treatment interaction was eliminated after controlling for thigmotaxis. These results indicate that WIN affects thigmotaxis rather than spatial reference memory. More importantly, these findings indicate a dissociation between the developmental effects of THC and the synthetic CB1 receptor agonist, WIN 55212-2. We suggest that the role of thigmotaxis be carefully evaluated in future neurodevelopmental studies of spatial learning, especially those investigating the endocannabinoid system.

Research highlights▶ WIN 55212-2 (1 mg/kg) was found to affect adolescents and adults differently. ▶ Thigmotaxis was reduced on days 1 and 2 in adolescent but not adult animals. ▶ WIN 55212-2 affects thigmotaxis rather than spatial reference memory. ▶ The neurodevelopmental effect of WIN differs from those previously observed for Δ9-THC.