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.

Acute and chronic modulation of striatal endocannabinoid‐mediated plasticity by nicotine

“…Drug addiction is a chronic relapsing disorder that involves progressive adaptations of cortico-striatal Nicotine modulates eCB-LTDnetworks (Yin, Ostlund, & Balleine 2008;Belin et al 2009;Belin et al 2013;Adermark et al 2016), and the data presented here suggest that the eCB system might play a role in mediating these transformations. Even though no causal relationship with behavioral transformations was assessed in this study, it is possible that nicotine-induced facilitation of eCB signaling could promote neuroadaptations and contribute to the initial conditioning and motivational effects elicited by nicotine.…”

Reduced dopamine receptors and transporters but not synthesis capacity in normal aging adults: a meta-analysis

“…PHNO), or b) the sample was a subsample of another included study, or c) primarily consisted of smokers or relatives of Parkinson’s patients. Changes in the DA system have been linked with both smoking nicotine (Adermark et al, 2016; Subramaniyan and Dani, 2015) and genes associated with the DA system in Parkinson’s patients (Warner and Schapira, 2003). …”

Neuropeptide systems and new treatments for nicotine addiction

“…A brief period of nicotine intake can lead to changes in brain networks that cause compulsive drug taking (Adermark et al 2016; Bruijnzeel 2012). Smoking cessation leads to negative affective symptoms such as dysphoria, anxiety, and impaired cognitive function (Hughes et al 1991; Hughes and Hatsukami 1986).…”