Discriminative Stimulus Effects of Gabapentin

Abstract

Gabapentin (Neurontin) is synthetic analog of GABA that functions as a voltage‐gated calcium channel (VDCC) blocker and is FDA approved for the management of neuropathic pain and seizure disorders. While not a controlled substance, gabapentin misuse is associated with illicit opioid use, suggesting, along with anecdotal reports, that gabapentin may elicit positive subjective effects. The present study was conducted to examine the subjective effects of gabapentin using rats (N=10) trained to discriminate a 30.0 mg/kg dose of gabapentin (60 min pretreatment time) versus saline in a two‐choice drug discrimination task. The discrimination was acquired in all 10 animals (M = 67.4 sessions, +/− 7.2 SEM). A time course assessment using the gabapentin training dose revealed full substitution (> 80% Gabapentin‐appropriate responding) at 30 and 60 minutes post‐injection. In addition to the training dose, full substitution also occurred for a 60 and 120 mg/kg dose of Gabapentin. Full substitution was shown for the barbiturate and GABAA receptor positive modulator pentobarbital and for the gabapentin analog and VDCC blocker pregabalin. Partial substitution was shown with the psychostimulant d‐amphetamine and the anxiolytic drug and 5‐HT1A partial agonist buspirone. The present findings demonstrate gabapentin's discriminative stimulus effects appear to be primarily mediated by GABAA receptors and VDCC blockade and partially mediated by dopamine and 5‐HT receptors. Full substitution by pentobarbital and partial substitution by amphetamine suggests the potential for positive subjective effects produced by gabapentin.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.