Doses of Pregabalin that Decrease Ethanol Intake Potentiate the Disruptive Effects of Ethanol on Learning in Outbred Rats

Abstract

Alcohol abuse is a serious public health concern, with over three million Americans suffering from an alcohol use disorder annually. Currently available therapeutics for treating alcohol use disorder have limited clinical effectiveness; as such, there is a pressing need for new treatments. Pregabalin (Lyrica®), a voltage‐gated calcium channel inhibitor, has garnered interest as a potential therapeutic to help reduce alcohol intake and maintain abstinence in patients with alcohol use disorder. However, the data supporting such an indication are lacking and there do not appear to be any published studies investigating whether pregabalin can alter the acute effects of alcohol on learning and memory. The purpose of this study was twofold: 1) determine doses of pregabalin that decrease ethanol‐ and food‐maintained responding, and 2) test the hypothesis that doses of pregabalin that decrease ethanol intake will also alter the disruptive effects of ethanol on complex acquisition and performance behavior. Two separate groups of adult Long‐Evans rats were used for these studies. The first group of rats (n=9) responded under a multiple fixed‐ratio 10, variable‐interval 80‐sec schedule of ethanol (32% v/v) and food (45‐mg pellets) reinforcement, respectively. The second group (n=12) responded under a multiple schedule of repeated acquisition and performance of response sequences in which responding in both components was maintained by food reinforcement under a second‐order fixed‐ratio 3 schedule. In the first group, 18 – 180 mg/kg (i.p.) of pregabalin dose‐dependently decreased both ethanol‐ and food‐maintained responding, as well as post‐session blood ethanol concentrations; however, food‐maintained responding was more potently decreased than ethanol‐maintained responding. This lack of selectivity of pregabalin for reducing ethanol intake was further complicated by the effects of pregabalin and ethanol on the acquisition and performance task. In the second group, ethanol alone (0.56 – 2.37 g/kg, i.p.) dose‐dependently decreased response rates and increased percent errors in both the acquisition and performance components, although acquisition was more sensitive to disruption than performance. Furthermore, when doses of pregabalin (18 – 100 mg/kg, i.p.) that had no effect alone under this baseline were administered prior to ethanol, the dose‐effect curves for both response rate and accuracy were shifted leftward (i.e., smaller doses of ethanol were needed to decrease response rates and increase percent errors). These findings indicate that pregabalin can decrease ethanol intake, but that these doses will likely decrease responding for other reinforcers and potentiate the disruptive effects of ethanol on complex acquisition and performance behaviors. As such, pregabalin might not be useful in treating patients with alcohol use disorder even if they are already abstinent from alcohol because there is an increased risk of negative health consequences.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.