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

• 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

Subject headings

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Neurologi (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Neurology (hsv//eng)

Keyword

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

Publication and Content Type

ref (subject category)

art (subject category)