Journal Article

Temporal Rewiring of Striatal Circuits Initiated by Nicotine

Lotfi, Amir, Danielsson, Klara, Ulenius, Lisa, Morud, Julia, Söderpalm, Bo, Adermark, Louise, Ericson, Mia

2016

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Abstinence / Addictions / Addictive behaviors / Animals / area / Behavior / behavioral sensitization / Clinical Medicine / Cocaine / cocaine seeking / Corpus Striatum - drug effects / d-3 receptor expression / Disease Models, Animal / Dopamine / Dopamine - metabolism / dorsal striatum / dorsomedial striatum / Goals / In Vitro Techniques / induced dopamine release / Klinisk medicin / Locomotion - drug effects / locomotor sensitization / Male / Microdialysis / Nerve Net - drug effects / Nerve Net - ultrastructure / Neurochemistry / neurons / Neurosciences / Neurosciences & Neurology / Nicotine / Nicotine - pharmacology / Nicotinic Agonists - pharmacology / Original / Patch-Clamp Techniques / Pharmacology & Pharmacy / Physiology / Psychiatry / rat nucleus-accumbens / Rats / Rats, Wistar / Receptors, Dopamine - genetics / Receptors, Dopamine - metabolism / RNA, Messenger - metabolism / Silver Staining / Statistics, Nonparametric / Time Factors / Tobacco Use Disorder - pathology / ventral tegmental