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Progressive modulation of accumbal neurotransmission and anxiety-like behavior following protracted nicotine withdrawal

Artikel i vetenskaplig tidskrift
Författare Julia Morud
Joakim Strandberg
Anna Andrén
Mia Ericson
Bo Söderpalm
Louise Adermark
Publicerad i Neuropharmacology
Volym 128
Sidor 86-95
ISSN 0028-3908
Publiceringsår 2018
Publicerad vid Institutionen för neurovetenskap och fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för fysiologi
Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 86-95
Språk en
Länkar doi.org/10.1016/j.neuropharm.2017.1...
Ämnesord Anxiety-like behavior, Elevated plus-maze, GABA, Nicotine, Nucleus accumbens, Withdrawal, 4 aminobutyric acid A receptor, diazepam, animal experiment, animal tissue, anxiety, Article, behavior, controlled study, elevated plus maze test, ex vivo study, GABAergic transmission, gene expression, male, nerve cell plasticity, nerve excitability, neuromodulation, nonhuman, priority journal, rat, smoking cessation, synaptic transmission
Ämneskategorier Neurologi

Sammanfattning

Due to the highly addictive properties of nicotine, a low percentage of users successfully maintain cessation for longer periods of time. This might be linked to neuroadaptations elicited by the drug, and understanding progressive changes in neuronal function might provide critical insight into nicotine addiction. We have previously shown that neurotransmission in the nucleus accumbens (nAc), a key brain region with respect to drug reinforcement and relapse, is suppressed for as long as seven months after a brief period of nicotine treatment. Studies were therefore performed to define the temporal properties of these effects, and to assess behavioral correlates to altered neurotransmission. Ex vivo electrophysiology revealed progressive depression of synaptic efficacy in the nAc of rats previously receiving nicotine. In addition, following three months of nicotine withdrawal, the responses to GABAA receptor modulating drugs were blunted together with downregulation of several GABAA receptor subunits. In correlation to reduced accumbal neurotransmission, a reduced anxiety-like behavior; assessed in the elevated plus-maze and marble burying tests, were identified in animals pre-treated with nicotine. Lastly, to test the causal relationship between suppressed excitability in the nAc and reduced anxiety-like behavior, rats received local administration of diazepam in the nAc while monitoring behavioral effects on the elevated plus-maze. These results show that nicotine produces long-lasting changes in the GABAergic system, which are observed first after extended withdrawal. Our data also suggest that nicotine produces a progressive suppression of accumbal excitability, which could result in behavioral alterations that may have implications for further drug intake. © 2017

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Utskriftsdatum: 2019-10-21