Cannabidiol modulates the brain rhythms within the hippocampal-prelimbic pathway in reinstatement of extinguished methamphetamine-induced conditioned place preference

Neuroscience. 2026 Sep 18:S0306-4522(26)00637-8. doi: 10.1016/j.neuroscience.2026.09.025. Online ahead of print.

ABSTRACT

This study explores the neural mechanisms underlying the communication between the hippocampus and the prelimbic cortex during the reinstatement phase of reward-seeking behavior in a conditioned place preference (CPP) paradigm. Rats were exposed to methamphetamine (METH) [0.5 and 0.25 mg/kg] and the impact of these doses on neural oscillations within and between the hippocampus and the prelimbic cortex was investigated. Interestingly, no significant modulation was observed in the prelimbic area. Phase-amplitude coupling analysis demonstrated that METH administration influenced the interaction between hippocampal αβ (Alpha 8-12 Hz, Beta: 13-30 Hz) phases and the prelimbic βγ (Beta: 13-30 Hz, Gamma: 30-100 Hz) amplitudes, providing evidence for modulation of the prelimbic oscillations by the hippocampus during reward-seeking behavior. CBD administration led to a decrease in βγ oscillations power within the hippocampus, suggesting a potential modulation of the addictive drive. Furthermore, CBD attenuated the phase coupling between hippocampal αβ phases and prelimbic γ amplitudes, suggesting a potential role in altering neural dynamics. Notably, CBD decreased the strength of sustained αβ oscillations in the hippocampus, providing insights into its potential to prevent relapses. Overall, this experiment offers insights into neural mechanisms of drug-induced reinstatement, highlighting CBD’s potential for managing addiction-related brain oscillations and guiding future research on addiction intervention strategies.

PMID:42759806 | DOI:10.1016/j.neuroscience.2026.09.025