Gabapentin and D-cycloserine alone and in combination with naloxone in methadone-maintained humans responding under a naloxone novel-response discrimination procedure

The present study examined the impact of the N-type calcium channel blocker gabapentin (GBP) and the partial glycine agonist D-cycloserine (CYC) to attenuate the behavioral effects of naloxone in opioid-dependent humans responding under a naloxone discrimination procedure. Methadone-maintained participants were trained to distinguish between a low dose of naloxone (0.15 mg/70 kg, i.m.; i.e., drug A) and placebo (i.e. drug B) under an instructed novel-response drug discrimination procedure, in which participants identify the drug condition as 'A', 'B', or 'N' (neither A nor B - 'novel'). Once the discrimination was acquired, doses of CYC (0, 500, and 625 mg) and GBP (0, 100, 200, and 400 mg) each alone and in combination with the training dose of naloxone were tested. GBP alone produced only placebo-appropriate responding and did not significantly alter naloxone discrimination when coadministered with naloxone, though it modestly reduced naloxone-induced visual analog scale ratings of drug 'strength'. CYC alone also produced predominantly placebo-appropriate responding and did not modulate naloxone-appropriate responding, but increased ratings of bad effects and decreased ratings of like placebo relative to naloxone alone at the 500 mg dose. These null findings regarding the modulation of naloxone discrimination highlight the limited efficacy of GBP and CYC in this context, contributing to the understanding of pharmacological interactions with opioid antagonists and their potential implications for opioid withdrawal treatment.