Neuropeptides as mediators of the early-life impact on the brain; implications for alcohol use disorders

Abstract

The brain is constantly exposed to external and internal input and to function in an ever-changing environment we are dependent on processes that enable the brain to adapt to new stimuli. Exposure to postnatal environmental stimuli can interfere with vital adaption processes and cause long-term changes in physiological function and behavior. Early-life alterations in brain function may result in impaired ability to adapt to new situations, in altered sensitivity to challenges later in life and thereby mediate risk or protection for psychopathology such as alcohol use disorders (AUD). In clinical research the studies of mechanisms, mediators, and causal relation between early environmental factors and vulnerability to AUD are restricted and attempts are made to find valid animal models for studies of the early-life influence on the brain. This review focuses on rodent models and the effects of adverse and naturalistic conditions on peptide networks within the brain and pituitary gland. Importantly, the consequences of alcohol addiction are not discussed but rather neurobiological alterations that can cause risk consumption and vulnerability to addiction. The article reviews earlier results and includes new data and multivariate data analysis with emphasis on endogenous opioid peptides but also oxytocin and vasopressin. These peptides are vital for developmental processes and it is hypothesized that early-life changes in peptide networks may interfere with neuronal processes and thereby contribute the individual vulnerability for AUD. The summarized results indicate a link between early-life rearing conditions, opioids, and ethanol consumption and that the ethanol-induced effects and the treatment with opioid antagonists later in life are dependent on early-life experiences. Endogenous opioids are therefore of interest to further study in the early-life impact on individual differences in vulnerability to AUD and treatment outcome.

Is the rodent maternal separation model a valid and effective model for studies on the early-life impact on ethanol consumption?

“…These groups differ in a number of aspects and care must be taken in choosing the proper control depending on the question asked. Modified from (Nylander and Roman 2012). NH , non-handling; AFR , animal facility rearing; MS0 , brief handling of the pup with less than 1 min loss of contact with the dam; MS15 and MS180-360 , maternal separation for 15 min or 180–360 min, common protocols utilize 180, 240 or 360 min separations…”

“…These studies also include prolonged MS and they have not only provided valuable knowledge about neurobiological and behavioural consequences of early-life experiences but also about experimental factors that influence these effects (e.g. reviews by Kuhn and Schanberg 1998; Lehmann and Feldon 2000; Levine 2002; Macri and Würbel 2006; Nylander and Roman 2012; Pryce and Feldon 2003). …”

Involvement of the endogenous opioid system in the psychopharmacological actions of ethanol: the role of acetaldehyde

“…The opioid peptide precursors proopiomelanocortin (POMC), proenkephalin (PENK) or prodynorphin (PDYN) (Kieffer and Gavériaux-Ruff, 2002) are the source for the respective peptides β-endorphin, enkephalin, and dynorphin (Nylander and Roman, 2012). These endogenous ligands activate G-protein-coupled µ-, ∂-, and κ-opioid receptors (OR) (µ-OR, ∂-OR and κ-OR), which differ in their affinities and response profiles (Evans et al, 1992; Knapp et al, 1995; Kieffer and Evans, 2009).…”

Molecular Mechanisms of Neurodevelopmental Alterations in Prenatal and Neonatal Periods

“…Наиболее чувствительными к действию внешних факторов (в т.ч. социального харак-тера) являются пре-и ранний постнатальный периоды развития мозга у млекопитающих [4].…”