Maternal care‐related differences in males and females rats’ sensitivity to ethanol and the associations between the GABAergic system and steroids in males

Abstract

This study investigated the effect of maternal care on adolescent ethanol consumption, sensitivity to ethanol-induced hypnosis, as well as gonadal hormones and γ-aminobutyric acid type-A (GABA ) systems. Long Evans rat dams were categorized by maternal licking/grooming (LG) frequency into High- and Low-LG mothers. Both female and male offspring from Low-LG rats demonstrated a greater sensitivity to ethanol-induced hypnosis in the loss-of-righting-reflex test at ethanol doses of 3.0 and 3.5 g/kg during late-adolescence (postnatal Day 50) but not at mid-adolescence (postnatal Day 42). However, we found no effect of maternal care on consumption of a 5% ethanol solution in a two-bottle choice test. We further investigated the association between the observed variations in sensitivity to ethanol-induced hypnosis and baseline hormonal levels in males. In male offspring from Low-LG mothers compared to High-LG mothers, baseline plasma corticosterone and progesterone levels were higher. GABA α1 and δ subunit expressions were also higher in the cerebral cortex of Low-LG males but lower in the cerebellar synaptosomal fraction. Early environmental influences on adolescent sensitivity to ethanol-induced hypnosis, consumption, and preference may be mediated by gonadal hormones and possibly through GABAergic functions.

Stress, sensitive periods, and substance abuse

“…Modulation of passive behavior demonstrated by guinea pigs in the absence of the mother can be remediated by the presence of the dam and mimicked by lipopolysaccharide (a challenge that engages an immune response) (Hennessy et al, 2013). The dam further buffers maternal separation effects on sexual behavior (Popoola and Cameron, 2018).…”

G protein‐coupled receptor 158 modulates sensitivity to the sedative‐hypnotic effect of ethanol in male mice

“…Harmful alcohol use accounts for approximately 3,000,000 deaths worldwide per year and is involved in the etiology of liver, esophageal, and laryngeal cancers (Anderson, 2021; Bagnardi et al, 2001; Turati et al, 2013). Individual sensitivity to the sedative‐hypnotic effect of ethanol (EtOH) can be defined as the capacity to tolerate alcohol or the predisposition to be sedated, which is shaped by many factors such as psychological, environmental, and biological factors (Aguayo et al, 2014; Naassila et al, 2002; Popoola & Cameron, 2018; Schuckit, 2018; Thiele et al, 2000). The studies on EtOH sensitivity may facilitate uncovering the mechanism underlying harmful alcohol use and alcohol use disorder (AUD) in the clinic, of which the neurobiological substrates are far from clear.…”

“…After being absorbed into the circulation, EtOH is firstly degraded into acetaldehyde by alcohol dehydrogenase (ADH) and then metabolized into acetate by acetaldehyde dehydrogenase (ALDH) in the liver (Aguayo et al, 2014; Guillot et al, 2019; Thiele et al, 2000). EtOH can pass the blood–brain barrier (BBB) to interact with the CNS and influence the psychological state (Popoola & Cameron, 2018; Schuckit, 2018; Thiele et al, 2000). EtOH can disinhibit dopaminergic neurons by acting on the mesocorticolimbic system including the prefrontal cortex (PFC), ventral tegmental area (VTA), and nucleus accumbens (NAc), while EtOH at a high dose may non‐specifically suppress cortical excitation and cause sedation (Pal et al, 2018; San Martin et al, 2021; Vore et al, 2021).…”