Repeated Δ-9-Tetrahydrocannabinol administration dose dependently increases stablished schedule-induced drinking

Esmeralda Fuentes-Verdugo, Ricardo Pellón & Miguel Miguéns

The study investigates the impact of repeated Δ9-THC (tetrahydrocannabinol) administration on compulsive behaviour, specifically focusing on schedule-induced polydipsia (SID) as a potential animal model for compulsivity. The findings reveal that Δ9-THC administration resulted in increased licking behaviour in animals when administered at a dose of 5 mg/kg, but not at a higher dose of 10 mg/kg, which had no significant effect. Additionally, both doses of Δ9-THC led to a general decrease in magazine entries, a behaviour associated with seeking reinforcement, particularly as the sessions progressed. Contrary to previous findings suggesting cannabinoids’ potential to reduce compulsive behaviours, this study found that Δ9-THC increased compulsive licking. The study also highlights the complex dose-response relationship of cannabinoids, often exhibiting an inverted U-shaped curve across various behavioural parameters. The effects of Δ9-THC on schedule-induced drinking (SID) performance seem to vary depending on the timing and duration of administration. Acute administration of Δ9-THC appeared to reduce compulsive behaviour shortly after administration, while chronic administration resulted in the delayed acquisition of SID and increased compulsive behaviour once the behaviour was established. These findings suggest that Δ9-THC’s effects on compulsive behaviour are influenced by the timing and duration of exposure, as well as the dose. The study also discusses the neurobiological mechanisms underlying Δ9-THC’s effects on compulsive behaviour, particularly its interactions with the endocannabinoid system and its impact on synaptic transmission. Chronic Δ9-THC exposure is associated with decreased CB1 receptor numbers and altered synaptic plasticity, which may contribute to the observed effects on compulsive behaviour. Furthermore, the study explores the temporal pattern of compulsive licking behaviour and its modulation by Δ9-THC administration. Δ9-THC-treated animals displayed persistent licking during inter-food intervals, suggesting the development of habit-like behaviours. This persistence in licking behaviour may compete with other behaviours, such as magazine entries, leading to decreased occurrence. The study concludes that repeated Δ9-THC administration affects compulsive behaviour in a dose-dependent manner, with increases in compulsive licking observed only at specific doses. However, Δ9-THC is not suggested as a beneficial treatment for compulsive symptoms associated with SID based on these findings. Additionally, the study emphasizes the importance of considering the gender-specific effects of cannabinoids in future research. In summary, the study sheds light on the complex relationship between THC exposure and compulsive behaviour, highlighting the need for further research to understand better the specific dose-dependent effects of cannabinoids in various behavioural paradigms.