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Temporal Rewiring of Striatal Circuits Initiated by Nicotine

Artikel i vetenskaplig tidskrift
Författare Louise Adermark
Julia Morud
Amir Lotfi
Klara Danielsson
Lisa Ulenius
Bo Söderpalm
Mia Ericson
Publicerad i Neuropsychopharmacology
Volym 41
Nummer/häfte 13
Sidor 3051-3059
ISSN 0893-133X
Publiceringsår 2016
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 3051-3059
Språk en
Länkar dx.doi.org/10.1038/npp.2016.118
Ämnesord induced dopamine release, d-3 receptor expression, ventral tegmental, area, rat nucleus-accumbens, behavioral sensitization, dorsal striatum, locomotor sensitization, dorsomedial striatum, cocaine seeking, neurons, Neurosciences & Neurology, Pharmacology & Pharmacy, Psychiatry
Ämneskategorier Klinisk medicin

Sammanfattning

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.

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