L-DOPA and naloxone decrease nicotine preference in C. elegans

Nicotine is a highly addictive drug that is associated with numerous negative health outcomes and remains a significant public issue. Current nicotine addiction treatments remain insufficient, with high noncompliance and relapse rates. This study explores the potential of three FDA-approved drugs that may have clinical relevance to treat nicotine addiction. We used Caenorhabditis elegans (C. elegans) as a model organism to investigate the effects of levodopa (L-DOPA), naloxone (NXN), and N-acetylcysteine (NAC) on nicotine preference. Nicotine preference was assessed using a behavioral chemotaxis choice assay, where C. elegans were placed in the middle of an agar well and allowed to move either to an area with nicotine (Zone A) or vehicle (Zone B). In this study, 30 minute pretreatment with the dopamine precursor L-DOPA decreased nicotine preference. Similarly, a 30 minute pretreatment with the opioid receptor antagonist NXN decreased nicotine preference. However, neither 30 minute pretreatment nor chronic pretreatment with the antioxidant NAC affected nicotine preference. The current results provide preliminary evidence that both L-DOPA and NXN may be promising pharmacotherapies for reducing nicotine preference and helping individuals fight nicotine addiction. Future studies are therefore needed to evaluate this clinical potential, especially in a chronic nicotine exposure setting.