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Gestational Restraint Stress and the Developing Dopaminergic System: An Overview

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Abstract

Prenatal stress exerts a strong impact on fetal brain development in rats impairing adaptation to stressful conditions, subsequent vulnerability to anxiety, altered sexual function, and enhanced propensity to self-administer drugs. Most of these alterations have been attributed to changes in the neurotransmitter dopamine (DA). In humans; dysfunction of dopaminergic system is associated with development of several neurological disorders, such as Parkinson disease, schizophrenia, attention-deficit hyperactivity disorder, and depression. Evidences provided by animal research, as well as retrospective studies in humans, pointed out that exposure to adverse events in early life can alter adult behaviors and neurochemical indicators of midbrain DA activity, suggesting that the development of the DA system is sensitive to disruption by exposure to early stressors. The purpose of this article is to provide a general overview of published studies and our own study related to the effect of prenatal insults on the development of DA metabolism and biology, focusing mainly in articles involving prenatal-restraint stress protocols in rats. We will also attempt to make a correlation between theses alterations and DA-related pathological processes in humans.

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Abbreviations

6-OHDA:

6-Hydroxydopamine

AADC:

l-Amino acid decarboxylase

AAS:

Androgenic-anabolic esteroids

ACTH:

Adrenocorticotropic hormone

ADHD:

Attention-deficit hyperactivity disorder

AMG:

Amygdala

COMT:

Catechol-O-methyltransferase

CPu:

Caudate putamen

CPu-L:

Caudate putamen lateral

CPu-M:

Caudate putamen medial

CRH:

Corticotropin-releasing hormone

DA:

Dopamine

DAT:

DA transporter

DFC:

Dorsal frontal cortex

DOPAC:

3,4-Dihydroxyphenylacetic acid

E:

Embryonic day

EAAT:

Excitatory amino acid transporter

GLT:

Glutamate transporter

HPA:

Hypothalamic–pituitary–adrenal

HPG:

Hypothalamic–pituitary–gonadal

HVA:

Homovanillic acid

l-DOPA:

l-3,4-Dihydroxyphenylalanine

MAOB:

Monoamine oxidase B

mdDA:

Mesodiencephalic dopaminergic

mGluR:

Metabotropic glutamate receptor

MPC:

Medial prefrontal cortex

NAc:

Nucleus accumbens

NAc-C:

Nucleus accumbens core

NAc-S:

Nucleus accumbens shell

NMDA:

N-methyl-d-aspartic acid

PD:

Parkinson’s disease

PFC:

Prefrontal cortex

PND:

Postnatal days

POA:

Preoptic area

PS:

Prenatal stress

SN:

Substantia nigra

SNc:

Substantia nigra pars compacta

TH:

Tyrosine hydroxylase

TF:

Transcription factors

VGluT2:

Vesicular transporter of glutamate

VMAT2:

Vesicular monoamine transporter 2

VTA:

Ventral tegmental area

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The authors wish to thank Mrs. Susana Buglione for the excellent bibliographic management.

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Correspondence to Marta C. Antonelli.

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María R. Katunar, Ezequiela Adrover and María Eugenia Pallarés contributed equally to this work.

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Baier, C.J., Katunar, M.R., Adrover, E. et al. Gestational Restraint Stress and the Developing Dopaminergic System: An Overview. Neurotox Res 22, 16–32 (2012). https://doi.org/10.1007/s12640-011-9305-4

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