Maternal exposure to Δ9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central μ opioid receptors in adult offspring female rats

Vela, Gema; Martı́n, Sonsoles; Garcı́a-Gil, Lucı́a; Crespo, José Antonio; Ruiz‐Gayo, Mariano; Fernández-Ruiz, J.J.; García-Lecumberri, Carmen; Pélaprat, Didier; Fuentes, José A.; Ramos, J.A.; Ambrosio, Emilio

doi:10.1016/s0006-8993(98)00766-5

Cited by 153 publications

(128 citation statements)

References 41 publications

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“…However, prenatal THC exposure has been shown to induce sex-dependent changes of the mu opioid receptor binding in several brain regions including the amygdala and caudate-putamen in the adult brain. 34 In the Figure 5 The opioid receptors mRNA expression levels in the in the alcohol-exposed group (gray bar) expressed as a percentage of the control (white bar) in distinct brain regions. **Po0.01.…”

Section: Discussionmentioning

confidence: 99%

“…Alcohol-induced decrease of mu is not unexpected and elevation of the mu in amygdala is also consistent with animal studies. 34 It is important to emphasize that many cannabis subjects were also exposed to alcohol, nevertheless the cannabis-induced elevation of the mu expression was still evident in the human fetal amygdala. The effects of prenatal cannabis and alcohol exposure are expected to have, for example, different dose range and time course of their effects.…”

Section: Discussionmentioning

confidence: 99%

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Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

et al. 2006

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Fetal development is a period sensitive to environmental influences such as maternal drug use. The most commonly used illicit drug by pregnant women is marijuana. The present study investigated the effects of in utero marijuana exposure on expression levels of opioid-related genes in the human fetal forebrain in light of the strong interaction between the cannabinoid and opioid systems. The study group consisted of 42 midgestation fetuses from saline-induced voluntary abortions. The opioid peptide precursors (preprodynorphin and preproenkephalin (PENK)) and receptor (mu, kappa and delta) mRNA expression were assessed in distinct brain regions. The effect of prenatal cannabis exposure was analyzed by multiple regression controlling for confounding variables (maternal alcohol and cigarette use, fetal age, sex, growth measure and post-mortem interval). Prenatal cannabis exposure was significantly associated with increased mu receptor expression in the amygdala, reduced kappa receptor mRNA in mediodorsal thalamic nucleus and reduced preproenkephalin expression in the caudal putamen. Prenatal alcohol exposure primarily influenced the kappa receptor mRNA with reduced levels in the amygdala, claustrum, putamen and insula cortex. No significant effect of prenatal nicotine exposure could be discerned in the present study group. These results indicate that maternal cannabis and alcohol exposure during pregnancy differentially impair opioid-related genes in distinct brain circuits that may have long-term effects on cognitive and emotional behaviors.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

et al. 2006

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“…morphine) as an antinociceptive agent is greater in male than in female rodents and monkeys (45,46). Perinatal exposure to opioid drugs produced changes in binding and density of opioid receptor that differed regionally and that were mostly different as a function of sex (47). Sex-related differences in the experience of both clinically and experimentally induced pain have been widely reported (48).…”

Section: Discussionmentioning

confidence: 99%

Mouse μ Opioid Receptor Distal Promoter Transcriptional Regulation by SOX Proteins

Hwang

Wang

et al. 2003

Journal of Biological Chemistry

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We have identified transcription factors that bind to specific sequences in 5 -distal promoter regulatory sequences of the mouse opioid receptor (mor) promoter using the yeast one-hybrid system. The sequence between ؊746 and ؊707 in mor distal promoter was used as the bait because it acts as a functional promoter element and binds several DNA-binding proteins. From an adult mouse brain cDNA library, five cDNA clones encoding three Sox gene family (Sry like high mobility group (HMG) box gene) transcriptional factors, mSOX18, mSOX21, and mSOX6, were isolated. Electrophoretic mobility shift assays confirmed the presence of a binding site for SOX proteins in the ؊731/؊725 region. Additionally, we have also established that the flanking regions outside the core Sox-binding site play an essential role in high affinity binding. DNase I footprint analysis indicates that proteins from mouse brain interact with the Sox-binding site within the mor distal promoter. Finally, we demonstrated that overexpression of mSOX18 and/or mSOX21 was able to up-regulate mouse mor distal promoter activity in mor-expressing neuronal cells (NMB). These data indicate that SOX proteins might contribute to the transcriptional activity of the mor gene and suggest that opioid receptor could mediate some of the developmental processes in which SOX proteins are included.Opioids have many pharmacological and physiological effects, including analgesia, sedation, euphoria, and respiratory depression and also induce tolerance and physical dependence when administered chronically. Pharmacological, physiological, receptor binding, and molecular cloning studies (1) have revealed that opioids interact with three major types of opioid receptors in the mammalian central nervous system and peripheral tissues, , ␦, and . All three types of receptors belong to the superfamily of G-protein-coupled receptors (2), and the opioid receptor (mor) 1 is known to play the essential role in morphine-induced analgesia, tolerance, and dependence as indicated from pharmacological studies. This has also been confirmed by additional in vivo pharmacological analyses of mice where mor was deleted by homologous recombination (3).Mor is expressed mainly in the central nervous system, where it exhibits distinct temporal and spatial patterns of distribution (1). Recently, in situ hybridization studies and other methods (e.g. RPA (RNase protection assay) and reverse transcriptase-PCR) indicate that expression of mor mRNA is regulated at the transcriptional level, especially during embryonic development (4 -7). The molecular mechanisms underlying this regulation are not completely understood, but analysis of the 5Ј-upstream sequences from the translation initiation sites of the mor gene has shown that expression of mor is driven by two promoters, a distal and a proximal promoter (8). Both promoters exhibit characteristics of housekeeping genes lacking a TATA box (9, 10), with the proximal promoter regulating mor transcription from four major initiation sites located in a region 291-...

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“…Developmental studies (Rodriguez de Fonseca et al 1993) have previously demonstrated a sexual dimorphic pattern of CB 1 receptors arising in prenatal striata. Prenatal exposure to cannabinoid agonists modifies μ-OR density, and it differs with the sex of the animal (Perez-Rosado et al 2000;Vela et al 1998), leading to the possibility of differences established before birth in the CB 1 (−/−) genotype that might lead to a sexually dimorphic character when behaviors are tested as adults.…”

Section: Sexual Dimorphic Effects Of Cannabinoidsmentioning

confidence: 99%

Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex

et al. 2008

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Rationale-Endocannabinoid, opioid, and dopamine systems interact to exhibit cannabinoid receptor neuromodulation of opioid peptides and D 4 dopamine receptor gene expression in CB 1 -cannabinoid-deficient mouse striatum.Objective-Using CB 1 -transgenic mice, we examine primary age-sex influences and interactions on opioid and dopamine system members' gene expression in striatum. Results-(1) Increased PPENK and PPDYN, owing to genotype [CB 1 (+/+) vs. CB 1 (−/−)], depended on sex. When genotype-independent, they depended on sex (PPENK) or age (PPDYN).(2) δ-OR was age-dependent (higher in old). (3) μ-OR, owing to genotype, was age-dependent [higher in old CB 1 (−/−) males]. When genotype-independent, it depended on sex (higher in NIH Public Access Author ManuscriptPsychopharmacology (Berl). Author manuscript; available in PMC 2013 July 11.

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Maternal exposure to Δ9-tetrahydrocannabinol facilitates morphine self-administration behavior and changes regional binding to central μ opioid receptors in adult offspring female rats

Cited by 153 publications

References 41 publications

Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

Discrete opioid gene expression impairment in the human fetal brain associated with maternal marijuana use

Mouse μ Opioid Receptor Distal Promoter Transcriptional Regulation by SOX Proteins

Gene expression of opioid and dopamine systems in mouse striatum: effects of CB1 receptors, age and sex

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