Pre‐ and postnatal alcohol exposure delays, in female but not in male rats, the extinction of an auditory fear conditioned memory and increases alcohol consumption

Abstract

Repeated exposure to alcohol increases retrieval of fear‐conditioned memories, which facilitates, among other factors, the emergence of post‐traumatic stress disorder (PTSD). Individuals with PTSD are more likely to develop alcohol and substance abuse related disorders. We assessed if prenatal and early postnatal alcohol exposure (PAE) increased the susceptibility to retain aversive memories and if this was associated with subsequent heightened alcohol consumption. Pregnant Sprague‐Dawley rats were exposed for 22 hr/day, throughout pregnancy and until postnatal Day 7 to a single bottle of sucralose ‐ sweetened 10% alcohol solution (PAE Group), or to a single bottle of tap water and sucralose (Control Group). Auditory fear conditioning (AFC) was performed in the adolescent offspring at postnatal Day 40. Freezing was measured during acquisition, retention and extinction phases, followed by 3 weeks of free choice alcohol intake. Female, but not male, PAE rats exhibited impaired extinction of the aversive memory, a finding associated with higher levels of 3‐4 Dihidroxyphenylacetic acid (DOPAC) in the nucleus accumbens and heightened alcohol intake, respect to controls. These findings suggest that PAE makes females more vulnerable to long‐term retention of aversive memories, which coexist with heightened alcohol intake. These findings are reminiscent of those of PTSD.

Prenatal Ethanol Exposure Misregulates Genes Involved in Iron Homeostasis Promoting a Maladaptation of Iron Dependent Hippocampal Synaptic Transmission and Plasticity

“…Regarding the function of VTA in PAE animals, we previously described that NOX2 inhibition, a synaptic enzyme that synthesizes superoxide in the VTA, restored alcohol-conditioned place preference in PAE animals (Contreras et al, 2017). Moreover we detected higher DOPAC levels, a dopamine metabolite, in the VTA terminals of nucleus accumbens of PAE animals (Plaza et al, 2019). However, the mechanism involved in iron homeostasis and the particular role of Iron in VTA function of PAE animals will be a matter to be addressed in future studies.…”

Exercise reduces physical alterations in a rat model of fetal alcohol spectrum disorders

“…Jiang et al [ 43 ], recently described that the irisin level in serum, as well as brain irisin levels decrease proportionally with time of ethanol consumption and even with the percentage of ethanol preference, moreover the levels of serum irisin have statistically significant correlation with poor performance in cognitive test (depressive and anxiety-like behaviors). Since PAE animals, especially the model that is used in this article, have cognitive alteration [ 44 – 46 ], together with alteration in motor skills, we hypothesize that PAE decreased irisin levels in a basal state. Contrary to our hypothesis, we observed weak but significantly higher levels of plasma irisin in PAE compared with control animals, however, resistance exercise, which improve the strength, does not change the levels in control or PAE animals.…”

Gestational ethanol exposure impairs motor skills in female mice through dysregulated striatal dopamine and acetylcholine function

“…Animals were anesthetized with isoflurane, the brains were removed, and 300 µm-thick coronal sections through the striatum were prepared (Leica VT1200S, Leica Biosystems, IL) in ice-cold carbogen-saturated (95% O 2 /5% CO 2 ) cutting solution (in mM: Sucrose 194, NaCl 30, KCl 4.5, MgCl 2 1, NaHCO 3 26, NaH 2 PO 4 1.2, Glucose 10). Slices were then transferred to a chamber filled with oxygenated artificial cerebrospinal fluid (aCSF) (pH 7.4) containing (in mM): NaCl (126), KCl (2.5), NaHCO 3 (25), NaH 2 PO 4 (1.2), dextrose (10), HEPES (20), CaCl 2 (2.4), MgCl 2 (1.2), and L-ascorbic acid (0.4) kept at 32 °C and allowed to recover for 1 h until used for recordings. After the equilibration period, brain slices were transferred to the recording chamber and perfused at a rate of ~1.5 mL/minute with aCSF.…”

“…In animal models of gestational ethanol exposure (GEE), female offspring show decreased behavioral inhibition [9] and impaired extinction of aversive memories compared to males [10]. While GEE interferes with cognitive and motor skill learning [11][12][13][14], sex-specific effects on motor function remain unclear.…”