Assessment of addiction behavior and spermatogenesis in glial cell line-derived neurotrophic factor-treated cannabis-addicted rats: An experimental study.

Abstract

Background: Cannabis addiction poses risks to male fertility by lowering levels of glial cell line-derived neurotrophic factor (GDNF), which is vital for spermatogenesis.

Objective: This research aimed to determine if the injection of exogenous GDNF into the brain of cannabis-addicted rats has a positive impact on their behavior and spermatogenesis.

Materials and methods: This study involved 15 male Wistar rats divided into 3 equal groups: control, model, and experimental. Cannabis addiction was induced in the model and experimental groups using a smoking machine with a 0.25 gr dose per 5 rats, and the experimental group received a 0.5 mg GDNF treatment via stereotaxic injection. Behavioral changes were assessed through plus maze, open field, and sucrose preference tests before and after treatments. Sperm parameters were evaluated with H&E staining, sperm morphology with Diff-Quik staining, DNA damage and viability with acridine orange and trypan blue staining.

Results: Addicted rats displayed increased anxiety, which was improved by GDNF treatment (p $<$ 0.05). Although cannabis significantly reduced germ cells and the size of the testis and epididymis compared to controls (p = 0.0006, p = 0.003), GDNF had a limited effect on these aspects. Cannabis significantly altered sperm morphology (p = 0.0016), but GDNF reversed abnormal sperms. GDNF improves sperm quality, reverses cannabis-induced sperm grading alterations (grade C, p = 0.0295), reduces DNA damage significantly (p = 0.0242), and enhances sperm viability, highlighting its potential to counteract some of cannabis's harmful effects on male reproductive health.

Conclusion: The findings of this experiment suggest that exogenous GDNF could be a potential therapeutic agent for cannabis addiction and sperm parameters.