Effects of Prenatal Ethanol Exposure on the Excitability of Ventral Tegmental Area Dopamine Neurons in Vitro

Wang, Jue; Haj‐Dahmane, Samir; Shen, Roh‐Yu

doi:10.1124/jpet.106.109041

Cited by 24 publications

(18 citation statements)

References 41 publications

(64 reference statements)

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“…As for molecular changes in the DA system, previous studies show that PAE causes a persistent reduction in the spontaneous electrical activity of midbrain DA neurons in adult mice (Choong & Shen, 2004b) and a lower frequency of evoked action potentials in VTA DA neurons, which could lead to decreased excitability (Wang, Haj-Dahmane, & Shen, 2006). Furthermore, an imbalance between D 1 and D 2 receptors has been found in the dorsolateral STR of PAE rats, impairing the development and maturation of corticostriatal synaptic plasticity (Zhou, Wang, & Zhu, 2012).…”

Section: Discussionmentioning

confidence: 99%

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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Background and Purpose Alcohol exposure in utero may lead to a wide range of long‐lasting morphological and behavioural deficiencies known as fetal alcohol spectrum disorders (FASD), associated with a higher risk of later developing neuropsychiatric disorders. However, little is known about the long‐term consequences of cocaine use and abuse in individuals with FASD. This study aimed to investigate the effects of maternal binge alcohol drinking during prenatal and postnatal periods on cocaine reward‐related behaviours in adult offspring. Experimental Approach Pregnant C57BL/6 female mice were exposed to an experimental protocol of binge alcohol consumption (drinking‐in‐the‐dark test) from gestation to weaning. Male offspring were subsequently left undisturbed until reaching adulthood and were tested for cocaine‐induced motivational responses (conditioned place preference, behavioural sensitization and operant self‐administration). Protein expression of dopamine‐ and glutamate‐related molecules was assessed following cocaine‐induced reinstatement. Key Results The results show that prenatal and postnatal alcohol exposure enhanced the preference for the cocaine‐paired chamber in the conditioned place preference test. Furthermore, early alcohol‐exposed mice displayed attenuated cocaine‐induced behavioural sensitization but also higher cocaine self‐administration. Furthermore, alterations in glutamatergic excitability (GluA1/GluA2 ratio) and ΔFosB expression were found in the prefrontal cortex and the striatum of alcohol‐exposed mice after cocaine‐primed reinstatement. Conclusion and Implications Our findings demonstrate that maternal binge‐like alcohol consumption during gestation and lactation alters sensitivity to the reinforcing effects of cocaine in adult offspring mice. Together, such data suggest that prenatal and postnatal alcohol exposure may underlie an enhanced susceptibility of alcohol‐exposed offspring to develop drug addiction later in adulthood.

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Section: Discussionmentioning

confidence: 99%

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Cantacorps

Montagud‐Romero

Luján

et al. 2020

British J Pharmacology

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“…Several studies have investigated the spontaneous impulse activity of VTA DA neurons after PE. An in vitro patch clamp study (Wang et al, 2006) shows that PE does not alter the impulse activity of VTA DA neurons. Conversely, a series of in vivo studies demonstrate that PE persistently decreases the impulse activity in VTA DA neurons (Shen et al, 1999;Xu and Shen, 2001;Choong and Shen, 2004a;Shen and Choong, 2006).…”

Section: Functional Implicationsmentioning

confidence: 94%

Excitatory Synaptic Function and Plasticity is Persistently Altered in Ventral Tegmental Area Dopamine Neurons after Prenatal Ethanol Exposure

Hausknecht

Haj‐Dahmane

Shen

et al. 2014

Neuropsychopharmacol

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Prenatal ethanol exposure (PE) is one of the developmental factors leading to increased addiction propensity (risk). However, the neuronal mechanisms underlying this effect remain unknown. We examined whether increased excitatory synaptic transmission in ventral tegmental area (VTA) dopamine (DA) neurons, which is associated with drug addiction, was impacted by PE. Pregnant rats were exposed to ethanol (0 or 6 g/kg/day) via intragastric intubation from gestational day 8-20. Amphetamine self-administration, whole-cell recordings, and electron microscopy were performed in male offspring between 2 and 12-week-old. The results showed enhanced amphetamine selfadministration in PE animals. In PE animals, we observed a persistent augmentation in calcium-permeable AMPA receptor (CP-AMPAR) expression, indicated by increased rectification and reduced decay time of AMPAR-mediated excitatory postsynaptic currents (AMPAREPSCs), enhanced depression of AMPAR-EPSCs by NASPM (a selective CP-AMPAR antagonist), and increased GluA3 subunits in VTA DA neuron dendrites. Increased CP-AMPAR expression in PE animals led to enhanced excitatory synaptic strength and the induction of CP-AMPAR-dependent long-term potentiation (LTP), an anti-Hebbian form of LTP. These observations suggest that, in PE animals, increased excitatory synaptic strength in VTA DA neurons might be susceptible to further strengthening even in the absence of impulse flow. The PE-induced persistent increase in CP-AMPAR expression, the resulting enhancement in excitatory synaptic strength, and CP-AMPAR-dependent LTP are similar to effects observed after repeated exposure to drugs of abuse, conditions known to increase addiction risk. Therefore, these mechanisms could be important neuronal substrates underlying PE-induced enhancement in amphetamine selfadministration and increased addiction risk in individuals with fetal alcohol spectrum disorders.

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“…PAE produces marked alterations in DA systems, including reductions in neuronal activity, receptor binding sites, and metabolites (Blanchard et al 1993, Shetty et al 1993, Spear 1996, Shen et al 1999, Wang et al 2006, Shen et al 2007), which alter tonic DA activity and change neurobiological sensitivity. For example, PAE attenuates the typical decrease in basal D 1 and D 2 expression in the nucleus accumbens (NAc) and striatum following chronic variable stress (Uban et al 2013) and the drug-induced increases in NAc DA content (Chen et al 1997), despite enhanced stimulant sensitization in these animals (Hannigan and Pilati 1991, Barbier et al 2009).…”

Section: Introductionmentioning

confidence: 99%

Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

et al. 2014

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Rationale Individuals with fetal alcohol spectrum disorder (FASD) are at increased risk for substance use disorders (SUD). In typically developing individuals, susceptibility to SUD is associated with alterations in dopamine and hypothalamic-pituitary-adrenal (HPA) systems, and their interactions. Prenatal alcohol exposure (PAE) alters dopamine and HPA systems, yet effects of PAE on dopamine-HPA interactions are unknown. Amphetamine-stress cross-sensitization paradigms were utilized to investigate sensitivity of dopamine and stress (HPA) systems, and their interactions following PAE. Methods Adult Sprague-Dawley offspring from PAE, pair-fed, and ad libitum-fed control groups were assigned to amphetamine-(1–2mg/kg) or saline-treated conditions, with injections every other day for 15 days. 14 days later, all animals received an amphetamine challenge (1mg/kg) and 5 days later, hormones were measured under basal or acute stress conditions. Amphetamine sensitization (augmented locomotion, days 1–29) and cross-sensitization with acute restraint stress (increased stress hormones, day 34) were assessed. Results PAE rats exhibited a lower threshold for amphetamine sensitization compared to controls, suggesting enhanced sensitivity of dopaminergic systems to stimulant-induced changes. Cross-sensitization between amphetamine (dopamine) and stress (HPA hormone) systems was evident in PAE, but not in control rats. PAE males exhibited increased dopamine receptor expression (mPFC) compared to controls. Conclusions PAE alters induction and expression of sensitization/cross-sensitization, as reflected in locomotor, neural, and endocrine changes, in a manner consistent with increased sensitivity of dopamine and stress systems. These results provide insight into possible mechanisms that could underlie increased prevalence of SUD, as well as the impact of widely prescribed stimulant medications among adolescents with FASD.

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Effects of Prenatal Ethanol Exposure on the Excitability of Ventral Tegmental Area Dopamine Neurons in Vitro

Cited by 24 publications

References 41 publications

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Prenatal and postnatal alcohol exposure increases vulnerability to cocaine addiction in adult mice

Excitatory Synaptic Function and Plasticity is Persistently Altered in Ventral Tegmental Area Dopamine Neurons after Prenatal Ethanol Exposure

Amphetamine sensitization and cross-sensitization with acute restraint stress: impact of prenatal alcohol exposure in male and female rats

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