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

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, but not 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 a sensitive assay by which to elucidate the molecular mechanisms and brain region-specific consequences of PCE, and facilitate the search for effective therapeutic solutions.

Illicit Drugs in Surface Waters: How to Get Fish off the Addictive Hook

“…While limited studies have been conducted on this topic, it is known that cocaine can induce various physiological changes in fish, such as altering heart rate and electrocardiogram parameters [ 169 ]. COC exposure has been shown to affect the dopaminergic system and anxiety levels in zebrafish, indicating its potential to modulate neurotransmitter function [ 170 , 171 ]. Cocaine is responsible for the blockage of the dopamine transporter, increasing the levels of dopamine in the synaptic cleft [ 127 ].…”

Prenatal drug exposure and neurodevelopmental programming of glucocorticoid signalling

“…Cocaine exposure influences epigenetic modifications such as DNA methylation, including in the prenatal setting, 57 as well as via alterations in histone acetylation that can lead to lasting effects on gene and protein expression remote to prenatal exposure . Although longitudinal studies evaluating these specific effects in progeny have yet to be completed with the aim of investigating the observed effects on the HPA axis, these modifications may represent potential mechanisms via which prenatal cocaine exposure alters HPA axis programming.…”