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

Abstract

Unlike Δ(9)-THC, the synthetic compound WIN 55212-2 (WIN) is a full agonist of endogenous cannabinoid receptors. Previous work has shown Δ(9)-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 (1mg/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.

Figure 1

Mean daily path length between the starting location and the hidden platform. WIN treated animals are identified by open markers and adolescents are identified by square markers. All animals learned across days. Collapsing across days, adolescents swam farther to reach the platform than adults. Adolescent controls swam the farthest. Data are presented in meters +/− SEM. □ indicates significantly different from adolescent WIN.

Figure 2

Mean daily path length within the outer most region (thigmotaxis). Group markers are identical to those in Figure 1. Thigmotactic distance declined across days for all animals but did so in an age by treatment dependent fashion. Adolescent controls swam farther in thigmotaxis on Day 1 & 2 than any other group. Data are presented in meters +/− SEM. □ indicates significantly different from adolescent WIN.