Abstract
BackgroundDocosanyl ferulate (DF) is a behaviourally active GABAA receptor complex (GABAAR) 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).AimsThe 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.MethodsIn 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 conclusionsThe 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 GABAARs 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.
Highlights
Drug addiction is defined as the progressive loss of control over drug taking caused by repeated exposures to addictive drugs
Previous studies have shown that Withania somnifera Dunal (WSE) prevents both ethanol (Spina et al 2015)- and morphine (Ruiu et al 2013)-elicited acquisition of conditioned place preference (CPP) as well as both ethanol- and morphineelicited CPP expression, i.e. the ability of environmental stimuli, conditioned to both ethanol (Spina et al 2015) and morphine (Ruiu et al 2013), to determine a positive sidepreference shift (CPP expression) at the post-conditioning test
As a follow-up of previous studies from our laboratory, the present investigation was aimed at (i) characterizing further the potentially beneficial application of WSE to counteract the ability of acutely administered ethanol (Ibba et al 2009; Porru et al 2020, 2021; Rosas et al 2017) and morphine (Rosas et al 2016) to increase extracellular signal-regulated kinases (ERKs) phosphorylation in the accumbens shell (AcbSh) and (ii) establishing whether WSE’s active compound, docosanyl ferulate (Maccioni et al 2021; Sonar et al 2019), may be responsible for such effects as well as for WSE’s effects on acquisition and expression of ethanol- and morphine-elicited CPP
Summary
Drug addiction is defined as the progressive loss of control over drug taking caused by repeated exposures to addictive drugs. 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 morphineelicited pERK in the AcbSh were evaluated by immunohistochemistry. These results highlight subtle but critical differences for the role of GABAARs 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
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