Effects of allyphenyline on chronic alcohol intoxication model

Alcohol withdrawal refers to a cluster of symptoms that may occur from suddenly ceasing the use of alcohol after chronic or prolonged ingestion. These symptoms make alcohol abstinence difficult and increase the risk of relapse in recovering alcoholics. Our study was aimed at identifying novel candidate compounds, which might attenuate alcohol withdrawal signs in the rat. In previous studies, we demonstrated that allyphenyline, endowed with effective adrenergic α2C-agonism/α2A-antagonism and serotoninergic 5-HT1A-agonism, significantly reduced morphine withdrawal syndrome and associated depression. Here, we evaluated the effects of allyphenyline on alcohol withdrawal signs in Wistar rats. For this purpose, animals were subjected to a 4-day chronic alcohol intoxication (by intragastric administration), and at 24 hours following cessation of alcohol exposure, they were treated intraperitoneally (ip) with allyphenyline (0.05 mg/kg and 0.5 mg/kg). Somatic withdrawal signs were scored after ip treatment. In a subsequent experiment, to evaluate the effects of allyphenyline on alcohol withdrawal-induced anxiety, another group of rats was subjected to ethanol intoxication and after 1 week was tested for anxiety behavior in the elevated plus maze (EPM) and in the defensive burying tests. The blood alcohol levels were assessed on third and fourth day of chronic alcohol intoxication. Results showed that allyphenyline did not reduce the expression of somatic withdrawal signs but attenuated anxiety-like behaviors in defensive burying tests associated with chronic alcohol intoxication. Allyphenyline did not affect anxiety scores in EPM. These findings suggest that modulation of the aforementioned receptor systems activity attenuates the expression of the affective but not the somatic signs during alcohol withdrawal.