The Effects of Adolescent WIN-55 Exposure

Assessing Changes in Neuroanatomy and Social Behaviour in Rats

Abstract

The effect of cannabis on adolescent development is a topical and socially relevant issue, as several states have moved to legalize its use, and with Canada seeming to follow suit.  Previous work in this field has found that adolescent exposure to cannabis can lead to deficits in the development of higher-level brain functions like attention and working memory (Ehrenreich et al., 1999). Because of the implication of cannabis exposure on the development of the adolescent brain, particularly regarding executive function skills, we believe studying play will serve as a benchmark from which we can begin to assess these changes. In order to do so, this study utilized WIN-55, a THC analogue and endocannabinoid (CB1) agonist that elicits comparable effects to those displayed following THC exposure (Schneider and Koch, 2003). Over the course of this study, animals were exposed to a daily dose of 0.3 mg/kg WIN-55, or a saline control for 10 days during puberty. Dosing encompassed postnatal day (P) 22-32 for females and P32-42 for males. We hypothesized that this dosing paradigm would be sufficient to elicit changes in the behaviour, ultrasonic vocalizations and neuroanatomy of the affected animals. Following the final injection, animals were socially isolated from their cage mate for 24hrs to encourage playful interaction during behavioural testing. The animals were then paired with their cage mate and placed in a dark, soundproof chamber where audio and video were recorded for 10 minutes. This procedure was replicated the following day so as to record a second day of behavioural analysis. Following all behavioural testing the animals were sacrificed and their brains extracted for anatomical analysis. Measures of neuroanatomy included thalamic volume and cortical thickness measurements, which were taken from selected planes of the brain. Stereological analysis was conducted on two frontal regions of the brain, AID and Cg3, which contribute to higher brain functioning. Adolescent play behaviour was recorded over peak-play periods and was analysed to reveal a significant decrease in the number of interactions between affected males. Ultrasonic vocalization analysis also revealed significant decreases in the number of calls exhibited in affected males. *Indicates presenter