Effects of Ethanol Exposure and Withdrawal on Neuronal Morphology in the Agranular Insular and Prelimbic Cortices: Relationship with Withdrawal-Related Structural Plasticity in the Nucleus Accumbens.

Madeline E Frost,Veronica L Peterson,Brian Mccool,Derek A Hamilton,Clark W Bird

doi:10.3390/brainsci9080180

Abstract

The present study investigated the effects of chronic intermittent ethanol exposure and withdrawal on dendritic morphology and spine density in the agranular insular and prelimbic cortices. Adult male Sprague–Dawley rats were passively exposed to vaporized ethanol (~37 mg/L; 12 h/day) or air (control) for ten consecutive days. Dendritic length, branching, and spine density were quantified in layer II/III pyramidal neurons 24 hours or seven days following the final ethanol exposure. Compared to unexposed control animals there were structural alterations on neurons in the prelimbic cortex, and to a lesser extent the agranular insular cortex. The most prominent ethanol-related differences were the transient increases in dendritic length and branching in prelimbic neurons at 24 h post-cessation, and increased mushroom-shaped spines at seven days post-cessation. The results obtained in the prelimbic cortex are the opposite of those previously reported in the nucleus accumbens core (Peterson, et al. 2015), suggesting that these regions undergo distinct functional adaptations following ethanol exposure and withdrawal.

Highlights

Alcohol exposure and withdrawal induce robust modifications in dendritic length, branching, and spine density on neurons within circuits implicated in drug addiction and reward [1,2,3,4,5,6].Such structural modifications represent alterations in the space available for synaptic connections and are among the major neurobiological adaptations by which experience alters the brain in the service of future behavior [7,8,9]
Modifications in dendritic morphology following drug exposure and cessation may contribute to the constellation of behavioral and cognitive alterations observed during withdrawal [10,11,12,13,14]
The goal of the present study was to evaluate the effects of alcohol exposure and withdrawal on structural alterations in pyramidal neurons in two prefrontal cortical regions implicated in addiction, the agranular insular cortex (AID) and prelimbic cortex (PrL; Zilles’ area Cg3, [15])

Summary

Introduction

Alcohol exposure and withdrawal induce robust modifications in dendritic length, branching, and spine density on neurons within circuits implicated in drug addiction and reward [1,2,3,4,5,6].Such structural modifications represent alterations in the space available for synaptic connections and are among the major neurobiological adaptations by which experience alters the brain in the service of future behavior [7,8,9]. The goal of the present study was to evaluate the effects of alcohol exposure and withdrawal on structural alterations in pyramidal neurons in two prefrontal cortical regions implicated in addiction, the agranular insular cortex (AID) and prelimbic cortex (PrL; Zilles’ area Cg3, [15]) These regions display complementary changes in response to drug exposure and other forms of experience, such as stress [16,17,18], and are connected to the nucleus accumbens (NAc) core and shell, which have been implicated in drug seeking, reward learning, and reinforcement [19,20,21,22,23,24,25]. This pallidal region projects to the mediodorsal nucleus of the thalamus [32], which has strong reciprocal connections with PrL and AID [33]

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