The effect of concurrent application of the deep brain stimulation of the nucleus accumbens and cannabidiol injection during extinction period on reinstatement of METH-induced conditioned place preference in extinguished rats.

Methamphetamine (METH) is a potent stimulant drug that significantly alters the function of the central nervous system (CNS). METHS's abuse may be linked with a variety of psychiatric disorders, primarily by affecting the reward system. Cannabidiol (CBD), a primary cannabinoid component of the Cannabis plant, has been shown to affect the reward system, suggesting it for modulating addictive behaviors. On the other hand, deep brain stimulation (DBS) of the nucleus accumbens (NAc), one of the most significant brain regions implicated in mediating rewards, is effective in alleviating drug-seeking behaviors. The present research aimed to evaluate the effects of low-frequency DBS, CBD, and a combination of both on the extinction and reinstatement of METH-induced conditioned place preference (CPP). CBD was injected into the lateral ventricle at doses of 2.5, 5, and 10 μg/5 μL, and low-frequency DBS (10 Hz, for 30 minutes) was administered to the NAc, both during the extinction phase. The results showed CBD (10 µg/5 µL) or DBS facilitated extinction. DBS decreased mean extinction latency but did not differ significantly from CBD (10 µg/5 µL) alone. The combination groups at all tested CBD doses showed reduced mean extinction latency compared with the control groups; only the 10 µg/5 µL combination group differed significantly from DBS alone. However, neither CBD (10 µg/5 µL) alone nor DBS altered the CPP score on the reinstatement day. Combination of DBS and CBD administration (at all doses) significantly decreased the CPP score on the reinstatement day. In conclusion, it can be suggested that CBD may be beneficial for alleviating METH-induced reinstatement in combination with DBS, while both alone had no effect.