Discriminative Stimulus Effects of 30.0 and 300.0 mg/kg Gabapentin in Rats: Substitution Testing with Morphine and Fentanyl

Abstract

<b>Abstract ID 56087</b> <b>Poster Board 416</b> Gabapentin is a blocker for Ca2+ channels that contain an α2Δ-1 or α2Δ-2 subunit and is prescribed for neuropathic pain, anxiety, fibromyalgia, and epilepsy. There are increasing reports of abuse with gabapentin, particularly when also used with opioids. These observations suggest that gabapentin may produce positive subjective effects and that these effects may be similar, to some extent, with opioids. In order to examine the subjective effects of gabapentin, the present study utilized a drug discrimination procedure in 22 male adult Sprague Dawley rats trained to discriminate either a 30.0 (30GPN) or 300.0 mg/kg dose (300GPN) of gabapentin versus saline in a two choice operant task for food reinforcement. All rats met the training criteria, consisting of 5 out 6 consecutive sessions of at least 80% condition-appropriate responding. Gabapentin produced full-substitution (&gt;80% drug-lever responding) for 30GPN beginning at a 15.0 mg/kg dose and for 300GPN beginning at a 100.0 mg/kg dose. Morphine produced partial substitution (&gt;20% drug-lever responding) for both training doses, with a 5.0 mg/kg dose of morphine producing partial substitution for both 30GPN (40.9% drug-lever responding) and 300GPN (31.7%). A 10.0 mg/kg dose of morphine also partially substituted for the lowest training dose, 30GPN (64.8%), which significantly reduced response rates (0.5 responses per second [RPS]), but this dose was highly rate suppressant for the 300GPN group (0.02 RPS), which precluded determination of percent drug responding for this dose. A 0.08 mg/kg dose of fentanyl partially substituted for 30GPN (45.6%) and for 300GPN (33.2%). Pretreatment with a 3.0 mg/kg dose of the opioid receptor antagonist naltrexone partially blocked the discriminative stimulus effects of 30GPN (69.5%) and 300GPN (69.8%). The present findings indicate that gabapentin can be readily established as a discriminative cue and that the properties of this cue may be partially mediated by opioid receptors.