Effects of Withania somnifera on oral ethanol self-administration in rats.

Recent evidence has shown that Withania somnifera Dunal (Ashwagandha or Indian ginseng), a herbal remedy used in traditional medicine, impairs morphine-elicited place conditioning. Here, we investigated the effect of W. somnifera roots extract (WSE) on motivation for drinking ethanol using operant self-administration paradigms. Wistar rats were trained to self-administer ethanol (10%) by nose-poking. The effects of WSE (25-75 mg/kg) were evaluated on acquisition and maintenance, on ethanol breakpoint under a progressive-ratio schedule of reinforcement and on the deprivation effect and reinstatement of seeking behaviours. Moreover, on the basis of the recent suggestion of an involvement of GABAB receptors in WSE central effects, we studied the interaction between WSE and GABAB ligands. The effect of WSE on saccharin (0.05%) oral self-administration was also tested. The results show that WSE reduced the acquisition, maintenance and breakpoint of ethanol self-administration. WSE also reduced the deprivation effect, reinstatement of ethanol-seeking behaviours and saccharin reinforcement. Furthermore, the GABAB receptor antagonist, phaclofen, counteracted the ability of WSE to impair the maintenance of ethanol self-administration. These findings show that WSE, by an action that may involve GABAB receptors, impairs motivation for drinking ethanol and suggest that further investigations should be performed to determine whether W. somnifera may represent a new approach for the management of alcohol abuse.

Alpha-lipoic acid reduces ethanol self-administration in rats.

BACKGROUND: The main system of central ethanol (EtOH) oxidation is mediated by the enzyme catalase. By reacting with H2 O2 , brain catalase forms compound I (the catalase-H2 O2 system), which is able to oxidize EtOH to acetaldehyde (ACD) in the brain. We have previously shown that ACD regulates EtOH motivational properties and possesses reinforcing effects by itself. In this study, we investigate the effects of alpha-lipoic acid (ALA), a scavenging agent for H2 O2 , on oral EtOH self-administration. METHODS: To this end, we trained Wistar rats to orally self-administer EtOH (10%) by nose poking. The effect of intraperitoneal pretreatment with ALA was evaluated during (i) maintenance of EtOH self-administration, (ii) EtOH self-administration under a progressive ratio (PR) schedule of reinforcement, and (iii) oral EtOH priming to induce reinstatement of EtOH seeking behavior. Moreover, we tested the effect of ALA on saccharin (0.05%) reinforcement, as assessed by oral self-administration. RESULTS: The results indicate that ALA dose-dependently reduced the maintenance, the break point of EtOH self-administration under a PR and the reinstatement of EtOH seeking behavior without suppressing saccharin self-administration. CONCLUSIONS: These results support that ALA may have a potential use in alcoholism treatment.