title: Acetylcholine, drug reward and substance use disorder treatment: intra- and interindividual striatal and accumbal neuron ensemble heterogeneity may explain apparent discrepant findings.
abstract: Converging evidence from different independent laboratories suggests that acetylcholine may play an important role in drug reward and that modulation of the cholinergic system may be useful for the treatment of substance use disorders. In this commentary, we try to reconcile apparently discrepant animal behavioral, human behavioral and clinical data with a unifying hypothesis positing that the modulation of drug-versus natural stimuli-mediated reward by cholinergic interneurons in the nucleus accumbens (and the dorsal striatum) is restricted to distinct neuron ensembles that show considerable intra- and interindividual variation with respect to their spatial distribution. The precise targeting of these interindividually variable neuron ensembles would be a prerequisite for a successful pharmacotherapy based on the modulation of the cholinergic system. We also provide experimental data to support our unifying hypothesis.
authors.affiliation: Experimental Psychiatry Unit, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Janine M
authors.initials: JM
authors.lastname: Prast
authors.forename: Kai K
authors.initials: KK
authors.lastname: Kummer
authors.forename: Constanze M
authors.initials: CM
authors.lastname: Barwitz
authors.forename: Christian
authors.initials: C
authors.lastname: Humpel
authors.forename: Georg
authors.initials: G
authors.lastname: Dechant
authors.forename: Gerald
authors.initials: G
authors.lastname: Zernig
mesh_terms: D000109:Acetylcholine / Q000502:physiology*; D000818:Animals; D001479:Basal Ganglia / Q000502:physiology*; D003042:Cocaine; D003213:Conditioning, Psychological / Q000502:physiology; D051766:Early Growth Response Protein 1 / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward; D019966:Substance-Related Disorders / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D003042:Cocaine; D000109:Acetylcholine