Adolescent Δ⁹-THC Exposure Differentially Affects Mice Depending on Their Personality

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• Adolescence is a critical period for brain development.
• Exposure to Δ⁹-tetrahydrocannabinol (THC) during adolescence can cause lasting neurobehavioral changes.
• Existing research on adolescent THC exposure yields conflicting results regarding long-term effects.

Purpose of the Study:

• To investigate the role of individual differences in stress-coping abilities in mediating the long-term effects of adolescent THC exposure.
• To determine if stress resilience or vulnerability influences neurobehavioral outcomes following adolescent THC exposure.

Main Methods:

• Used selectively bred Dominant (stress-resilient) and Submissive (stress-vulnerable) mice.
• Administered THC or vehicle to adolescent mice and assessed behaviors in adulthood.
• Evaluated anxiety-like behavior, exploratory behavior, recognition memory, and sensitivity to NMDA receptor hypofunction (MK-801-induced locomotion).

Main Results:

• THC differentially affected anxiety and exploration based on stress vulnerability: it increased exploration and reduced anxiety in Sub mice, while producing opposite effects in Dom mice.
• Recognition memory showed minor, line-dependent alterations.
• Adolescent THC exposure potentiated MK-801-induced locomotion in Dom mice but attenuated it in Sub mice, indicating altered NMDA receptor function.

Conclusions:

• Stress-vulnerability traits are a significant factor influencing the neurobehavioral consequences of adolescent THC exposure.
• These findings highlight the importance of considering individual stress-coping differences in preclinical and translational research on adolescent cannabis use.
• Results suggest that stress resilience/vulnerability may predict differential long-term outcomes of adolescent cannabis exposure.