Novel anticonvulsants for reducing alcohol consumption: A review of evidence from preclinical rodent drinking models

Abstract

Alcohol use disorders (AUDs) are a major public health issue and have an enormous social and economic burden in developed, developing, and third-world countries. Current pharmacotherapies for treating AUDs suffer from deleterious side effects and are only effective in preventing relapse in a subset of individuals. This signifies an essential need for improved medications to reduce heavy episodic drinking and alcohol-related problems. Growing literature has provided support for the use of anticonvulsants in suppressing symptoms induced by alcohol withdrawal. Emerging clinical and preclinical evidence suggests that a number of well-tolerated anticonvulsants may also decrease alcohol drinking. This review will focus on recent evidence supporting the efficacy of novel anticonvulsants in reducing voluntary alcohol consumption in rodent models. The data demonstrate that anticonvulsants reduce drinking in standard home cage two-bottle choice paradigms, self-administration of alcohol in operant chambers, and cue- and stress-induced reinstatement of alcohol seeking behaviors in rats and mice. This review also highlights evidence that some anticonvulsants were only moderately effective in reducing drinking in select strains of rodents or models. This suggests that genetics, possible neuroadaptations, or the pharmacological target affect the ability of anticonvulsants to attenuate alcohol consumption. Nonetheless, anticonvulsants are relatively safe, have little abuse potential, and can work in combination with other drugs. The results from these preclinical and clinical studies provide compelling evidence that anticonvulsants are a promising class of medication for the treatment of AUDs.

Keywords: alcohol; anticonvulsants; consumption; novel pharmacotherapy; rodent models.

Figure 1

The K_Ca2.2/3 channel positive modulator CyPPA reduces drinking and alcohol preference in a 24 hr intermittent access mouse model. (A) Escalation of voluntary alcohol consumption across 10 drinking sessions [one-way RM ANOVA, F(9,63) = 24.426, p < 0.001, Student Newman-Keuls (SNK) post-hoc test, *p < 0.01 vs. session 1, **p < 0.001 vs. sessions 1 & 2, ***p < 0.001 vs. sessions 1, 2 & 3 n=8 mice], (B) Administration of CyPPA (30 mg/kg, IP) 30 min prior to the start of the drinking session significantly reduces alcohol consumption at the 6 and 24 hr time points compared with vehicle treated mice [two-way ANOVA, F(2,24) = 3.601, p < 0.05, SNK post hoc, *p < .05 vs. vehicle, n = 4-6/group]. (C) CyPPA (30 mg/kg) treatment also significantly reduces preference for alcohol at both time points [F(2,27) = 9.44, p < 0.001, SNK post-hoc, *p < .01 vs. vehicle & 15 mg/kg].