PUBLICATION

Prenatal cocaine exposure disrupts the dopaminergic system and its postnatal responses to cocaine

Authors

Riley, E., Maymi, V., Pawlyszyn, S., Lili, Y., Zhdanova, I.V.

ID

ZDB-PUB-171107-12

Date

2017

Source

Genes, brain, and behavior 17(4): e12436 (Journal)

Registered Authors

Zhdanova, Irina

Keywords

DAT, behavior, cocaine, dopamine, dopamine receptor, dopamine transporter, knockout model, prenatal cocaine exposure, zebrafish

MeSH Terms

Larva/drug effects
Dopamine/metabolism
Dopaminergic Neurons/drug effects*
Dopaminergic Neurons/metabolism
Neurons/metabolism
Cocaine/administration & dosage
Cocaine/toxicity*
Male
Dopamine Plasma Membrane Transport Proteins/metabolism
Zebrafish
Female
Animals
Brain/drug effects
Brain/metabolism
Dopamine Uptake Inhibitors/administration & dosage
Receptors, Dopamine D1/metabolism*

(all 16)

PubMed

29105298 Full text @ Genes Brain Behav.

Abstract

Impaired attention is the hallmark consequence of prenatal cocaine exposure (PCE), affecting brain development, learning, memory and social adaptation starting at an early age. To date, little is known about the brain structures and neurochemical processes involved in this effect. Through focusing on the visual system and employing zebrafish as a model, we show that PCE reduces expression of dopamine receptor Drd1, with levels reduced in the optic tectum and other brain regions, except the telencephalon. Organism-wide, PCE results in a 1.7-fold reduction in the expression of the dopamine transporter (dat), at baseline. Acute cocaine administration leads to a 2-fold reduction in dat in drug-naive larvae but not PCE fish. PCE sensitizes animals to an anxiogenic-like behavioral effect of acute cocaine, bottom-dwelling, while loss of DAT due to genetic knockout (DATKO) leads to bottom-dwelling behavior at baseline. Neuronal calcium responses to visual stimuli in both PCE and DATKO fish show tolerance to acute cocaine in the principal regions of visual attention, the telencephalon and optic tectum. The zebrafish model can provide sensitive assay by which to elucidate the molecular mechanisms and brain region-specific consequences of PCE, and facilitate the search for effective therapeutic solutions.

Genes / Markers

Figures

Show all Figures

Expression

Phenotype

Fish	Conditions	Stage	Phenotype	Figure
WT	chemical treatment by environment: cocaine	Day 6	brain Ab2-drd1 labeling decreased amount, abnormal	Fig. 3
WT	chemical treatment by environment: cocaine	Day 6	cerebellum Ab2-drd1 labeling decreased amount, abnormal	Fig. 3
WT	chemical treatment by environment: cocaine	Day 6	optic tectum Ab2-drd1 labeling decreased amount, abnormal	Fig. 3
WT	chemical treatment by environment: cocaine	Days 7-13	behavior process quality, abnormal	Fig. 1
WT	lighting conditions, chemical treatment by environment: cocaine	Days 7-13	optic tectum response to light stimulus decreased process quality, abnormal	Fig. 4
slc6a3^{zf1089/zf1089}	control	Days 7-13	behavior process quality, abnormal	Fig. 1
slc6a3^{zf1089/zf1089}	chemical treatment by environment: cocaine	Days 7-13	behavior process quality, abnormal	Fig. 1
slc6a3^{zf1089/zf1089}	lighting conditions, chemical treatment by environment: cocaine	Days 7-13	optic tectum response to light stimulus process quality, ameliorated	Fig. 4

1 - 8 of 8

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Mutations / Transgenics

Allele	Construct	Type	Affected Genomic Region
nkGCaMPHS4aTg	Tg(UAS:GCaMPHS)	Transgenic Insertion
s1013tEt	Et(-1.5hsp70l:GAL4-VP16)	Transgenic Insertion
zf1089		Insertion	slc6a3

Human Disease / Model

Human Disease	Fish	Conditions	Evidence
substance-related disorder			TAS

Sequence Targeting Reagents

Fish

Antibodies

Orthology

Engineered Foreign Genes

Marker	Marker Type	Name
GAL4	EFG	GAL4
GCaMP	EFG	GCaMP

Mapping

Riley et al., 2017 ZDB-PUB-171107-12 PMID:29105298

Prenatal cocaine exposure disrupts the dopaminergic system and its postnatal responses to cocaine

Riley et al., 2017

ZDB-PUB-171107-12
PMID:29105298