Effects of docosanyl ferulate, a constituent of Withania somnifera , on ethanol- and morphine-elicited conditioned place preference and ERK phosphorylation in the accumbens shell of CD1 mice

Background Docosanyl ferulate (DF) is a behaviourally active GABA A receptor complex (GABA A R) agonist, recently isolated from the standardized methanolic extract of Withania somnifera Dunal ( WSE ) root. Previous studies have shown that WSE prevents both ethanol- and morphine-dependent acquisition and expression of conditioned place preference (CPP) and stimulation of dopamine release in the nucleus accumbens shell (AcbSh). Aims The study aimed at determining ( a ) whether DF contributes to WSE ’s ability to affect the acquisition and expression of ethanol- and morphine-elicited CPP and, given that phosphorylation of extracellular signal-regulated kinase (pERK) in the AcbSh is involved in associative learning and motivated behaviours, ( b ) whether WSE and DF may affect ethanol- and morphine-induced ERKs phosphorylation in the AcbSh. Methods In adult male CD1 mice, DF’s effects on the acquisition and expression of ethanol- and morphine-elicited CPP were evaluated by a classical place conditioning paradigm, whereas the effects of WSE and DF on ethanol- and morphine-elicited pERK in the AcbSh were evaluated by immunohistochemistry. Results and conclusions The study shows that DF, differently from WSE , affects only the acquisition but not the expression of ethanol- and morphine-induced CPP. Moreover, the study shows that both WSE and DF can prevent ethanol- and morphine-elicited pERK expression in the AcbSh. Overall, these results highlight subtle but critical differences for the role of GABA A Rs in the mechanism by which WSE affects these ethanol- and morphine-dependent behavioural and molecular/cellular responses and support the suggestion of WSE and DF for the control of different components of drug addiction.