Ghrelin Peptides Reduce Restlessness During Nicotine Withdrawal in Rats

Nicotine addiction remains a major global health crisis, with many individuals struggling to quit due to severe withdrawal symptoms. These symptoms often include irritability, anxiety, and significant changes in locomotor activity, making sustained abstinence challenging. While some pharmacotherapies exist, their efficacy is often limited, and relapse rates remain high. This study aimed to investigate whether the ghrelin system, known for its roles in reward and stress, could modulate acute nicotine withdrawal symptoms, specifically focusing on locomotor activity changes.

Acute nicotine withdrawal significantly increased locomotor activity in the control group, with total distance traveled increasing by 145% compared to non-withdrawn animals. Both Ghrelin and GHRP-6 treatments effectively attenuated this withdrawal-induced hyperactivity. Ghrelin administration reduced the withdrawal-induced increase in locomotor activity by 48% (p<0.01) compared to the saline-treated withdrawal group, bringing activity levels significantly closer to baseline. Similarly, GHRP-6 treatment resulted in a substantial 43% reduction (p<0.05) in withdrawal-induced locomotor activity. The effects of both peptides were observed within 15 minutes of administration and persisted throughout the 60-minute observation period, indicating a rapid and sustained amelioration of withdrawal symptoms. These findings suggest a crucial role for the ghrelin system in modulating the behavioral manifestations of nicotine withdrawal.