Increased expression of the Gaba B receptor gene during treatment with buprenorphine leads to methamphetamine tolerance in the lumbar spinal cord of rats

In response to psychostimulants, γ-aminobutyric acid type B receptor ( Gaba _B ) and G-protein-regulated inward-rectifier potassium channel 2 ( Girk ₂ ) are activated, causing dopaminergic neuronal excitability. Buprenorphine (BUP), an opioid with mixed agonist-antagonist activity, has been approved for opioid dependency treatment and as an analgesic. Reports suggest that µ receptor agonists, which open potassium channels in neurons, significantly relieve pain, possibly due to a connection with the Girk ₂ and Gaba _B receptors genes. This study examined methamphetamine (METH) addiction tolerance and changes in these gene expression levels during treatment with BUP. 16 groups of Wistar rats (n = 7) were randomly divided, including control, saline, METH (10 mg/kg), BUP (6 or 10 mg/kg), BUP (6 or 10 mg/kg) + METH, and withdrawal. A five- or fourteen-day intraperitoneal injection of BUP was given. After injections, a tail-flick test was performed. On the last day, these gene expressions were measured in the lumbar-spinal cord rats using qRT-PCR. These findings showed METH + BUP (10 mg/kg; 5 days) exhibited the greatest analgesia. Analgesia was enhanced after 5 days compared with 14 days. Gaba _B gene expression was also increased in the BUP + METH and BUP-alone groups. In the BUP group alone, Girk ₂ expression increased. It appears that tolerance develops with continued drug use, requiring higher doses to achieve the initial effect. However, higher doses are associated with a higher risk. Incremental expression of Gaba _B genes in BUP-related groups also denotes their association with analgesia. These genes are reduced in the METH-related groups.