Psychostimulant-Associated Reward, Reinforcement, and Habit Formation in Wild-Caught New Zealand Planaria

<p><strong>Substance use disorder (SUD) presents a major and rapidly evolving global health crisis, with severe consequences for individuals, communities, and healthcare systems. As the global drug addiction landscape grows in complexity, so too does the need for innovative research tools to explore the mechanisms driving drug abuse and relapse. Invertebrate models such as the flatworm Planaria offer unique advantages for this purpose. Their simple neurobiology combined with key similarities to vertebrates, such as conserved neurotransmitter systems and the capacity for reward-based learning, makes them an attractive upcoming model. Despite a growing literature base, prior research has mainly focused on Pavlovian conditioning, with limited exploration of operant conditioning or more complex addiction-related behavioural patterns such as habit formation. Moreover, psychostimulant behavioural research on planaria has focused largely on cocaine with little attention to the other major psychostimulant of abuse, methamphetamine. Furthermore, virtually no studies have explored the use of wild-caught planarian samples in behavioural experiments.</strong></p><p>To address these gaps, the present study investigated methamphetamine-associated conditioning, learning, and habit formation in wild-caught New Zealand planaria. We employed paradigms adapted from mammalian addiction research: conditioned place preference (CPP), and self-administration in the Y-maze. CPP findings showed that 10μM methamphetamine induced Pavlovian conditioning, which extinguished in absence of the drug and was promptly reinstated following brief re-exposure. In the Y-maze, reinforcement with 10μM methamphetamine produced operant drug-seeking behaviour, which was also responsive to extinction and reinstatement. Our habit formation experiments revealed that planaria overtrained on the operant Y-maze task displayed greater resistance to extinction and reduced sensitivity to reward devaluation. These phenomena are consistent with the transition from goal-directed to stimulus-response behaviour in the mammalian habit formation literature. Our findings provide the first evidence of drug-associated habit formation in invertebrates, and highlight the value and practicality of using wild-caught planarian species as cost-effective, accessible, and valid invertebrate models in addiction and other behavioural research. The study’s limitations are discussed, and recommendations made for future researchers to build upon our findings and improve our methodologies.</p>