Cocaine in Pregnancy

Plessinger, Mark A.; Woods, James R.

doi:10.1016/s0889-8545(05)70360-0

Cited by 32 publications

(4 citation statements)

References 117 publications

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“…Owing to its small size, the cocaine molecule can easily cross the placental barrier and enter the foetal blood system [1], producing a high risk of abortion, stillbirth, premature delivery, placental abruption, babies with low birth weight, as well as abnormalities in the liver, lungs, genitals and heart system [2], [3], [4], and in the nervous system [5], [6], [7], [8], [9], including changes in the dopaminergic signalling mechanism in the foetal brain [10], [11], [12], [13]. Moreover, several studies in humans and in animal models have confirmed that prenatal exposure to cocaine results in permanent changes at the behavioural, cellular and molecular levels [14], [15], [16].…”

Section: Introductionmentioning

confidence: 99%

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

et al. 2012

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The use of cocaine during pregnancy can affect the mother and indirectly might alter the development of the embryo/foetus. Accordingly, in the present work our aim was to study in vivo (in zebrafish embryos) the effects of cocaine on the expression of dopamine receptors and on miR-133b. These embryos were exposed to cocaine hydrochloride (HCl) at 5 hours post-fertilization (hpf) and were then collected at 8, 16, 24, 48 and 72 hpf to study the expression of dopamine receptors, drd1, drd2a, drd2b and drd3, by quantitative real time PCR (qPCR) and in situ hybridization (ISH, only at 24 hpf). Our results indicate that cocaine alters the expression of the genes studied, depending on the stage of the developing embryo and the type of dopamine receptor. We found that cocaine reduced the expression of miR-133b at 24 and 48 hpf in the central nervous system (CNS) and at the periphery by qPCR and also that the spatial distribution of miR-133b was mainly seen in somites, a finding that suggests the involvement of miR-133b in the development of the skeletal muscle. In contrast, at the level of the CNS miR-133b had a weak and moderate expression at 24 and 48 hpf. We also analysed the interaction of miR-133b with the Pitx3 and Pitx3 target genes drd2a and drd2b, tyrosine hydroxylase (th) and dopamine transporter (dat) by microinjection of the Pitx3-3'UTR sequence. Microinjection of Pitx3-3'UTR affected the expression of pitx3, drd2a, drd2b, th and dat. In conclusion, in the present work we describe a possible mechanism to account for cocaine activity by controlling miR-133b transcription in zebrafish. Via miR-133b cocaine would modulate the expression of pitx3 and subsequently of dopamine receptors, dat and th. These results indicate that miRNAs can play an important role during embryogenesis and in drug addiction.

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Section: Introductionmentioning

confidence: 99%

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

et al. 2012

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“…Studies in humans have revealed that prenatal cocaine exposure outcome in alterations of different organs (lungs, liver) and systems (the heart system [24]–[26] and the nervous system [27]–[30]). In spite of the efforts made to explain the mechanism of action of cocaine in the addiction process, no clear pathway has been found, that explains its effects.…”

Section: Introductionmentioning

confidence: 99%

Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

et al. 2012

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Prenatal exposure to cocaine, in mammals, has been shown to interfere with the expression of opioid receptors, which can have repercussions in its activity. Likewise, microRNAs, such as let-7, have been shown to regulate the expression of opioid receptors and hence their functions in mammals and in vitro experiments. In light of this, using the zebrafish embryos as a model our aim here was to evaluate the actions of cocaine in the expression of opioid receptors and let-7d miRNA during embryogenesis. In order to determine the effects produced by cocaine on the opioid receptors (zfmor, zfdor1 and zfdor2) and let-7d miRNA (dre-let-7d) and its precursors (dre-let-7d-1 and dre-let-7d-2), embryos were exposed to 1.5 µM cocaine hydrochloride (HCl). Our results revealed that cocaine upregulated dre-let-7d and its precursors, and also increased the expression of zfmor, zfdor1 and zfdor2 during early developmental stages and decreased them in late embryonic stages. The changes observed in the expression of opioid receptors might occur through dre-let-7d, since DNA sequences and the morpholinos of opioid receptors microinjections altered the expression of dre-let-7d and its precursors. Likewise, opioid receptors and dre-let-7d showed similar distributions in the central nervous system (CNS) and at the periphery, pointing to a possible interrelationship between them.In conclusion, the silencing and overexpression of opioid receptors altered the expression of dre-let-7d, which points to the notion that cocaine via dre-let-7 can modulate the expression of opioid receptors. Our study provides new insights into the actions of cocaine during zebrafish embryogenesis, indicating a role of miRNAs, let-7d, in development and its relationship with gene expression of opioid receptors, related to pain and addiction process.

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“…At the same time, blockade of uterine muscle norepinephrine uptake increases extracellular norepinephrine, which enhances uterine contraction. These effects on placental perfusion and uterine contraction were believed to be responsible for intrauterine growth retardation and premature delivery, which are often observed in women who abuse cocaine and amphetamines during pregnancy (Volpe, 1992; Plessinger and Woods, 1998; Plessinger, 1998; Kaltenbach, 2000; Addis et al, 2001). In addition, these drugs were thought to cross the placenta, most probably via diffusion.…”

Section: Effects Of Cocaine and Amphetamines On Pregnant Women – Pastmentioning

confidence: 99%

“…Since the normal function of the placenta is an absolute necessity for optimal growth and development of the fetus, interference in the functions of the placenta by pharmacologic agents will compromise fetal growth and development. It is well recognized that the drugs of abuse such as cocaine and amphetamines, when used by women during pregnancy, have significant detrimental effects not only on the mothers but also on their fetuses (Plessinger and Woods, 1998; Plessinger, 1998; Kaltenbach, 2000; Addis et al, 2001). But, the role of placenta in mediating these detrimental effects has not received much attention.…”

Section: Introductionmentioning

confidence: 99%

Drugs of abuse and human placenta

Ganapathy

2011

Life Sciences

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Drugs of abuse such as cocaine and amphetamines, when used by pregnant women, exert deleterious effects on the fetus. These drugs produce their effects through inhibition of the serotonin transporter, norepinephrine transporter, and dopamine transporter. The inhibition can occur in the pregnant mother as well as in the fetus. These events contribute to the detrimental effects of these drugs on the fetus. However, the role of placenta, which serves as the link between the pregnant mother and the fetus, in the process remains understudied. It has been assumed that placenta did not play any direct role in the process except that it allowed the passage of these drugs from maternal circulation into fetal circulation. This was before the discovery that placenta expresses two of the three monoamine transporters. The serotonin transporter and the norepinephrine transporter are expressed on the maternal-facing side of the syncytiotrophoblast, thus exposed to the inhibitory actions of cocaine and amphetamines if present in maternal blood. Inhibition of these transporters in placenta could lead to elevation of serotonin and norepinephrine in the intervillous space that may cause uterine contraction and vasoconstriction, resulting in premature delivery, decreased placental blood flow, and intrauterine growth retardation. Thus, the placenta is actually a direct target for these abusable drugs. Since the placental serotonin transporter and norepinephrine transporter are also inhibited by many antidepressants, therapeutic use of these drugs in pregnant women may have similar detrimental effects on placental function and fetal growth and development.

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Cocaine in Pregnancy

Cited by 32 publications

References 117 publications

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

Modulation by Cocaine of Dopamine Receptors through miRNA-133b in Zebrafish Embryos

Cocaine Modulates the Expression of Opioid Receptors and miR-let-7d in Zebrafish Embryos

Drugs of abuse and human placenta

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