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Review
. 2015 Jun 30;5(3):258-74.
doi: 10.3390/brainsci5030258.

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

Joan Y Holgate  1 , Selena E Bartlett  2
Affiliations
Review

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

Joan Y Holgate et al. Brain Sci. .

Abstract

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs. However, not everyone exposed to early life stress will develop an AUD. The mechanisms determining whether an individual's brain adapts and becomes resilient to the effects of stress or succumbs and is unable to cope with stress remain elusive. Emerging evidence suggests that neuroplastic changes in the nucleus accumbens (NAc) following early life stress underlie the development of AUDs. This review discusses the impact of early life stress on NAc structure and function, how these changes affect cholinergic signaling within the mesolimbic reward pathway and the role nicotinic acetylcholine receptors (nAChRs) play in this process. Understanding the neural pathways and mechanism determining stress resilience or susceptibility will improve our ability to identify individuals susceptible to developing AUDs, formulate cognitive interventions to prevent AUDs in susceptible individuals and to elucidate and enhance potential therapeutic targets, such as the nAChRs, for those struggling to overcome an AUD.

Keywords: Early life stress; GABA; alcohol; cholinergic; dopamine; mesolimbic; nicotinic acetylcholine receptors; nucleus accumbens; stress resilience.

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Figures

Figure 1
Figure 1
The stress response. Stressful events trigger the release of corticotrophin releasing hormone (CRH) from the hypothalamus which results in the release of adrenocorticotropic hormone (ACTH) from the pituitary into the blood. This causes glucocorticoids to be released from the adrenals which bind to glucocorticoid (GRs) and mineralocorticoid (MRs) receptors creating a negative feedback circuit, ending the stress response and restoring allostasis. Adapted from [22].
Figure 2
Figure 2
Nicotinic acetylcholine receptors (nAChRs) consist of different combinations of alpha (α) and beta (β) subunits. Variations in the subunit composition not only determine the number of binding sites for their endogenous ligand, acetylcholine (ACh) but also the functional properties of the receptor. Taken from [109].
Figure 3
Figure 3
Nicotinic acetylcholine receptors (nAChRs) are located within brain structures involved in modulating alcohol addiction and stress. nAChRs are found within the mesolimbic pathway (hippocampus, prefrontal cortex (PFC), nucleus accumbens (NAc), amygdala and ventral tegmental area (VTA)). These regions also express glucocorticoid receptors (GR) and participate in glutamatergic (blue), GABAergic (green), dopaminergic (red) and cholinergic (orange) neurotransmission. Adapted from [110].
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