PubMed: Hippocampal D1-like dopamine receptor as a novel target for the effect of cannabidiol on extinction and reinstatement of methamphetamine-induced CPP

PubMed: Hippocampal D1-like dopamine receptor as a novel target for the effect of cannabidiol on extinction and reinstatement of methamphetamine-induced CPP

Prog Neuropsychopharmacol Biol Psychiatry. 2024 May 8:111025. doi: 10.1016/j.pnpbp.2024.111025. Online ahead of print.

ABSTRACT

Methamphetamine (METH) is a major health problem without effective pharmacological treatment. Cannabidiol (CBD), a component of the Cannabis sativa plant, is believed to have the potential to inhibit drug-related behavior. However, the neurobiological mechanisms responsible for the effects of CBD remain unclear. Several studies have proposed that the suppressing effects of CBD on drug-seeking behaviors could be through the modulation of the dopamine system. The hippocampus (HIP) D1-like dopamine receptor (D1R) is essential for forming and retrieving drug-associated memory. Therefore, the present study aimed to investigate the role of D1R in the hippocampal CA1 region on the effects of CBD on the extinction and reinstatement of METH-conditioned place preference (CPP). For this purpose, different groups of rats over a 10-day extinction period were administered different doses of intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl, Saline) as a D1R antagonist before ICV injection of CBD (10 μg/5 μl, DMSO12%). In addition, a different set of animals received intra-CA1 SCH23390 (0.25, 1, or 4 μg/0.5 μl) before CBD injection (50 μg/5 μl) on the reinstatement day. The results revealed that the highest dose of SCH23390 (4 μg) significantly reduced the accelerating effects of CBD on the extinction of METH-CPP (P < 0.01). Furthermore, SCH23390 (1 and 4 μg) in the reinstatement phase notably reversed the preventive effects of CBD on the reinstatement of drug-seeking behavior (P < 0.05 and P < 0.001, respectively). In conclusion, the current study revealed that CBD made a shorter extinction period and suppressed METH reinstatement in part by interacting with D1-like dopamine receptors in the CA1 area of HIP.

PMID:38729234 | DOI:10.1016/j.pnpbp.2024.111025

https://pubmed.ncbi.nlm.nih.gov/38729234/?utm_source=Chrome&utm_medium=rss&utm_campaign=pubmed-2&utm_content=1Ds1JEbG0OWaBdqM3tTUGjkFhFGaOtMecPdpuvzbuubWi6d9Fn&fc=20231022105433&ff=20240511092229&v=2.18.0.post9+e462414 May 10, 2024 10:00 am