Andrén A, Adermark L, Söderpalm B, Ericson M (2019) An acetylcholine-dopamine interaction in the rat nucleus accumbens and its tentative involvement in ethanol’s dopamine-liberating effect. Neuroscience 2019 Abstracts 079.08. Society for Neuroscience, Chicago, IL.
Summary: Alcohol use disorder is a chronic, relapsing brain disorder associated with serious medical consequences leading to preterm death. Although few in number, cholinergic interneurons (CIN) have arisen as an important cell population within the nucleus accumbens (nAc) that may exert a regulatory impact on dopamine (DA) neurotransmission locally. A defect in CIN have been suggested to be involved in psychiatric diseases such as alcohol addiction. The mechanisms through which endogenous cholinergic activity modulates DA release in response to ethanol administration and its role in development of addiction is not known. In this project, the aim was to study if acetylcholine (ACh) can influence DA release locally in the nAc and if so, through which receptor population(s) this effect is mediated. Further, we wanted to determine the role of ACh in ethanol-induced DA elevation.Using reversed in vivo microdialysis, the acetylcholinesterase inhibitor physostigmine was administered locally in the nAc of male Wistar rats followed by addition of either the muscarinic ACh receptor inhibitor scopolamine or the nicotinergic ACh receptor inhibitor mecamylamine. Subsequently, ethanol was perfused following local pretreatment with scopolamine or mecamylamine, using the same methodology. An immunotoxin, anti-ChAT-saporine, was infused locally into the nAc of a subset of male Wistar rats to selectively lesion CIN, followed by local ethanol administration via reversed in vivo microdialysis. Local administration of physostigmine induced a DA elevation within the nAc, an effect blocked by scopolamine but not by mecamylamine. Local administration of ethanol increased DA levels. Scopolamine pretreatment non-significantly attenuated the ethanol-induced DA elevation, whereas pretreatment with mecamylamine had no effect. Preliminary results indicate a minor attenuation of the DA elevation observed after local administration of ethanol in toxin-treated animals, as compared to sham-treated controls. Taken together, these results suggest that ACh increases extracellular DA levels in nAc in vivo, an effect mediated by muscarinic ACh-receptors and not by nicotinic ACh-receptors. Considering that scopolamine moderately attenuated ethanol-induced DA output and that lesioning of CIN appeared to hamper DA release in response to ethanol, ACh release from CIN within the nAc may be partially involved in ethanol-induced DA release in nAc.
Related Products: Anti-ChAT-SAP (Cat. #IT-42)