Moderate Alcohol Exposure during the Rat Equivalent to the Third Trimester of Human Pregnancy Alters Regulation of GABAA Receptor-Mediated Synaptic Transmission by Dopamine in the Basolateral Amygdala

Abstract

Fetal ethanol (EtOH) exposure leads to a range of neurobehavioral alterations, including deficits in emotional processing. The basolateral amygdala (BLA) plays a critical role in modulating emotional processing, in part, via dopamine (DA) regulation of GABA transmission. This BLA modulatory system is acquired during the first 2 weeks of postnatal life in rodents (equivalent to the third trimester of human pregnancy) and we hypothesized that it could be altered by EtOH exposure during this period. We found that exposure of rats to moderate levels of EtOH vapor during the third trimester-equivalent [postnatal days (P) 2–12] alters DA modulation of GABAergic transmission in BLA pyramidal neurons during periadolescence. Specifically, D1R-mediated potentiation of spontaneous inhibitory postsynaptic currents (IPSCs) was significantly attenuated in EtOH-exposed animals. However, this was associated with a compensatory decrease in D3R-mediated suppression of miniature IPSCs. Western blot analysis revealed that these effects were not a result of altered D1R or D3R levels. BLA samples from EtOH-exposed animals also had significantly lower levels of the DA precursor (L-3,4-dihydroxyphenylalanine) but DA levels were not affected. This is likely a consequence of reduced catabolism of DA, as indicated by reduced levels of 3,4-dihydroxyphenylacetic acid and homovanillic acid in the BLA samples. Anxiety-like behavior was not altered in EtOH-exposed animals. This is the first study to demonstrate that the modulatory actions of DA in the BLA are altered by developmental EtOH exposure. Although compensatory adaptations were engaged in our moderate EtOH exposure paradigm, it is possible that these are not able to restore homeostasis and correct anxiety-like behaviors under conditions of heavier EtOH exposure. Therefore, future studies should investigate the potential role of alterations in the modulatory actions of DA in the pathophysiology of fetal alcohol spectrum disorders.

Third trimester-equivalent ethanol exposure increases anxiety-like behavior and glutamatergic transmission in the basolateral amygdala

“…delivered 2 hr apart; BEC = not determined but this paradigm is expected to produce high levels, near 0.5 g/dl; Ikonomidou et al, 2000) did not significantly alter performance in the elevated plus maze test during adulthood. Diaz et al, (2014a) found that moderate ethanol exposure in vapor chambers between P2 and P12 (BEC = 0.1 g/dl) does not significantly affect anxiety-like behavior during adolescence in rats. Therefore, whether ethanol exposure during the equivalent to the last trimester of human pregnancy affects anxiety-like behaviors remains an open question.…”

“…After exposure, offspring were allowed to grow until P36–50, when behavioral and electrophysiological experiments were conducted. Blood collection and determination of serum ethanol levels were performed as previously described (Diaz et al, 2014a). With the exception of blood ethanol determinations, only male rats were used for all experiments.…”

“…BLA slice preparation was done as previously described (Diaz et al, 2014a). Briefly, P36–50 rats were deeply anesthetized with ketamine (250 mg/kg i.p.)…”

Neonatal ethanol exposure from ethanol-based hand sanitisers in isolettes

“…In animal model, rat pups exposed to ethanol during the first week of life had all area of brain affected; the neurons of cerebellum and basolateral amygdala are especially damaged 22 24. These animals also showed behaviour problems after ethanol exposure 24. Preterm infants in isolettes are between 24 and 34 weeks of gestation.…”

Experimental models of early exposure to alcohol: a way to unravel the neurobiology of mental retardation

“…Two original research articles, hosted in this Research Topic, deal with amygdalar alterations in experimental FASD. Using a combination of biochemical, electrophysiological, and behavioral techniques, Fernando Valenzuela and coworkers demonstrated an impairment of dopamineregulated GABA neurotransmission in the basolateral amygdala (8). Cherry Ignacio, Sandra Mooney, and Frank Middleton (9) studied the micro-RNA expression in the amygdala of rats prenatally exposed to ethanol.…”