title: Temporal Rewiring of Striatal Circuits Initiated by Nicotine.
abstract: Drug addiction has been conceptualized as maladaptive recruitment of integrative circuits coursing through the striatum, facilitating drug-seeking and drug-taking behavior. The aim of this study was to define temporal neuroadaptations in striatal subregions initiated by 3 weeks of intermittent nicotine exposure followed by protracted abstinence. Enhanced rearing activity was assessed in motor activity boxes as a measurement of behavioral change induced by nicotine (0.36 mg/kg), whereas electrophysiological field potential recordings were performed to evaluate treatment effects on neuronal activity. Dopamine receptor mRNA expression was quantified by qPCR, and nicotine-induced dopamine release was measured in striatal subregions using in vivo microdialysis. Golgi staining was performed to assess nicotine-induced changes in spine density of medium spiny neurons. The data presented here show that a brief period of nicotine exposure followed by abstinence leads to temporal changes in synaptic efficacy, dopamine receptor expression, and spine density in a subregion-specific manner. Nicotine may thus initiate a reorganization of striatal circuits that continues to develop despite protracted abstinence. We also show that the response to nicotine is modulated in previously exposed rats even after 6 months of abstinence. The data presented here suggests that, even though not self-administered, nicotine may produce progressive neuronal alterations in brain regions associated with goal-directed and habitual performance, which might contribute to the development of compulsive drug seeking and the increased vulnerability to relapse, which are hallmarks of drug addiction.
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Louise
authors.initials: L
authors.lastname: Adermark
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Morud
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Amir
authors.initials: A
authors.lastname: Lotfi
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Klara
authors.initials: K
authors.lastname: Danielsson
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.|Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Lisa
authors.initials: L
authors.lastname: Ulenius
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.|Beroendekliniken, Sahlgrenska University Hospital, Gothenburg, Sweden.
authors.forename: Bo
authors.initials: B
authors.lastname: Söderpalm
authors.affiliation: Addiction Biology Unit, Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at The University of Gothenburg, Gothenburg, Sweden.
authors.forename: Mia
authors.initials: M
authors.lastname: Ericson
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D006040:Goals; D066298:In Vitro Techniques; D008124:Locomotion / Q000187:drug effects; D008297:Male; D017551:Microdialysis; D009415:Nerve Net / Q000187:drug effects* / Q000648:ultrastructure; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011954:Receptors, Dopamine / Q000235:genetics / Q000378:metabolism; D016622:Silver Staining; D018709:Statistics, Nonparametric; D013997:Time Factors; D014029:Tobacco Use Disorder / Q000473:pathology*
chemical_list: D018722:Nicotinic Agonists; D012333:RNA, Messenger; D011954:Receptors, Dopamine; D009538:Nicotine; D004298:Dopamine