Administration of the Synthetic Cannabinoid WIN55,212-2 Increases BDNF Expression Levels in the Adolescent Rat Brain

Abstract

Background:

The increase in cannabinoid use among adolescents has become a public health concern in North America, with more than one-third of 12th graders in the United States reporting consumption of some form of cannabis within the past year (2023).^1,2 The use of cannabinoids during adolescence, a vulnerable stage for brain development, may alter the neuroplasticity dependent on brain-derived neurotrophic factor (BDNF), ³ an essential protein for brain development. BDNF is found either as its precursor, pro-BDNF, involved in synaptic pruning and apoptosis, or its mature form (m-BDNF), which stimulates dendritic growth and cell survival. The synthetic cannabinoid Win55,212-2 (WIN) acts as a dual agonist for the endocannabinoid CB1 and CB2 receptors (eCBRs), emulating the psychotropic activity of Δ9-tetrahydrocannabinol. This study investigates the impact of WIN administration on levels of pro and m-BDNF in the adolescent brain (medial prefrontal cortex [mPFC], hippocampus, and cerebellar vermis[CbVr]) of adolescent male rats.

Methods:

Male adolescent Sprague–Dawley rats received two intraperitoneal injections, either WIN (0.8 mg/kg) or saline solution (0.9% NaCl) every 48 h, from postnatal day (PND) 30 to 37. On the final day (PND 38), a single injection of either WIN or saline was administered. The rat’s whole brain tissue was collected an hour after the last injection.

Results:

Chronic WIN administration during adolescence caused a significant increase in pro-BDNF levels in the brain’s CbVr and m-BDNF in the mPFC.

Conclusion:

Our findings suggest that chronic WIN administration can alter the baseline levels of pro and m-BDNF in the brains of male adolescent rats, which may have implications for synaptic plasticity and neurodevelopment.