Behavioral Effects of Gabapentin and Heroin in Rats

Abstract ID 87315 Poster Board 100 Gabapentin is a widely prescribed medication approved for the treatment of some seizure and neuropathic pain disorders and has long been considered a relatively safe drug with minimal toxicity or abuse potential. However, when used in conjunction with opioids, some individuals report prolonged or heightened effects of opioids. Also concerning are recent post-mortem studies that have detected gabapentin in up to 30% of opioid overdose deaths. Despite its extensive use in clinical settings, there is a notable scarcity of preclinical research examining the effects of gabapentin and potential interactions with opioids. This study had four goals, as follows: 1) characterize the behavioral effects of gabapentin in rats; 2) determine the onset and duration of these effects; 3) characterize interactions between gabapentin and heroin; and 4) determine whether there are sex differences in each of these outcomes. Male and female Sprague-Dawley rats (n = 7/sex) completed a battery of behavioral assessments (horizontal bar, inclined plane, and rotarod) and 27 common rodent behaviors were recorded and scored 0, 1, 2, 3, 5, and 7 hours following administration of gabapentin or saline. Heroin or saline was administered following the two-hour time point to evaluate interactions between drugs. The experimenter was blinded to all test conditions. Data for each behavioral assessment were compared across sex and drug condition. Gabapentin decreased performance on the rotarod test in a dose- and time-dependent manner and had no effect on the horizontal bar test. Conversely, heroin increased latency on the horizontal bar test and had no effect on the rotarod test. During the observation period, heroin exhibited a dose- and time-dependent reduction in overall activity and increased flat body posture and immobility. When gabapentin and heroin were administered together, the effects of heroin were both increased in magnitude and prolonged. There was a greater prolongation of effects in males and a greater enhancement of effects in females. Consistent with reports in humans, this study suggests that gabapentin can enhance the effects of opioids, particularly their effects on motor function and behavior. The apparent difference in the observed interactions between male and female rats underscores the importance of considering sex as a factor in future research investigating interactions between gabapentin and opioids. Future studies will determine whether gabapentinoids enhance other effects of opioids (e.g., reinforcing effects) and begin to determine the mechanism of the interaction between these drugs. Welch Foundation AQ-0039 NIH 1F31DA057832