Regulation of opioid gene expression in the rat brainstem by 3,4-methylenedioxymethamphetamine (MDMA): role of serotonin and involvement of CREB and ERK cascade

Benedetto, Manuela Di; Candia, Sussy del Carmen Bastías; D’Addario, Claudio; Porticella, Elena Elettra; Cavina, Chiara; Candeletti, Sanzio; Romualdi, Patrizia

doi:10.1007/s00210-010-0587-5

Cited by 13 publications

(7 citation statements)

References 67 publications

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“…We also investigated phospho-ERK 1/2 immunoreactivity, which has been reported elsewhere to be modulated by THC [39] and MDMA [40]. Changes in ERK1/2 phosphorylation have been associated with mood changes in animal models [41] and in our experimental setting, ERK1/2 signaling was down-regulated in the frontal cortex of adult male rats exposed to MDMA during the adolescence, although no significant effects were observed in females.…”

Section: Discussionmentioning

confidence: 67%

“…In order to correlate these behavioral responses with specific changes in intracellular signaling that may be promoted by THC and MDMA, we also measured the expression of the extracellular signal-regulated kinases 1 and 2 (ERK1/2), as well as that of the activity-regulated cytoskeletal-associated protein (Arc), both in the hippocampus and prefrontal cortex of these animals. ERK1/2 is believed to be modulated in the rat brain by chronic administration of THC [39] and MDMA [40], and these modifications have been related to changes in mood and anxiety-like behavior [41]. Similarly, Arc mRNA expression was modified by acute MDMA administration in the cortical and hippocampal regions of the rat [2], and this immediate early gene is translated to a cytosolic protein involved in synaptic plasticity, long-term potentiation and learning [42].…”

Section: Introductionmentioning

confidence: 99%

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Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

et al. 2013

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Ecstasy is a drug that is usually consumed by young people at the weekends and frequently, in combination with cannabis. In the present study we have investigated the long-term effects of administering increasing doses of delta-9-tetrahydrocannabinol [THC; 2.5, 5, 10 mg/kg; i.p.] from postnatal day (pnd) 28 to 45, alone and/or in conjunction with 3,4-methylenedioxymethamphetamine [MDMA; two daily doses of 10 mg/kg every 5 days; s.c.] from pnd 30 to 45, in both male and female Wistar rats. When tested one day after the end of the pharmacological treatment (pnd 46), MDMA administration induced a reduction in directed exploration in the holeboard test and an increase in open-arm exploration in an elevated plus maze. In the long-term, cognitive functions in the novel object test were seen to be disrupted by THC administration to female but not male rats. In the prepulse inhibition test, MDMA-treated animals showed a decrease in prepulse inhibition at the most intense prepulse studied (80 dB), whereas in combination with THC it induced a similar decrease at 75 dB. THC decreased hippocampal Arc expression in both sexes, while in the frontal cortex this reduction was only evident in females. MDMA induced a reduction in ERK1/2 immunoreactivity in the frontal cortex of male but not female animals, and THC decreased prepro-orexin mRNA levels in the hypothalamus of males, although this effect was prevented when the animals also received MDMA. The results presented indicate that adolescent exposure to THC and/or MDMA induces long-term, sex-dependent psychophysiological alterations and they reveal functional interactions between the two drugs.

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Section: Discussionmentioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

et al. 2013

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“…The discriminative stimulus effects of PCP were diminished by combination with LSD or MDMA in rats, presumably due to masking effects (7). A recent study showed that MDMA can regulate the endogenous κ-opioid system mediated by the activation of 5-HT 2 receptors (35). Therefore, it is possible that the hallucinogenic effects of U50,488H, PCP, MDMA, and LSD are mediated, at least in part, through the activation of 5-HT 2 receptors.…”

Section: Resultsmentioning

confidence: 99%

Discriminative Stimulus Effects of Hallucinogenic Drugs: a Possible Relation to Reinforcing and Aversive Effects

et al. 2012

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Abstract. The subjective effects of drugs are related to the kinds of feelings they produce, such as euphoria or dysphoria. One of the methods that can be used to study these effects is the drug discrimination procedure. Many researchers are trying to elucidate the mechanisms that underlie the discriminative stimulus effects of abused drugs (e.g., alcohol, psychostimulants, and opioids). Over the past two decades, the patterns of drug abuse have changed, so that club/recreational drugs such as phencyclidine (PCP), 3,4-methylenedioxymethamphetamine (MDMA), lysergic acid diethylamide (LSD), and ketamine, which induce perceptual distortions, like hallucinations, are now more commonly abused, especially in younger generations. However, the mechanisms of the discriminative stimulus effects of hallucinogenic drugs are not yet fully clear. This review will briefly focus on the recent findings regarding hallucinogenic/psychotomimetic drug-induced discriminative stimulus effects in animals. In summary, recent research has demonstrated that there are at least two plausible mechanisms that can explain the cue of the discriminative stimulus effects of hallucinogenic drugs; one is mediated mainly by 5-HT 2 receptors, and the other is mediated through sigma-1 (σ 1 )-receptor chaperone regulated by endogenous hallucinogenic ligand.

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“…It is has been reported that pERK1/2 regulates prodynorphin expression through c-Fos or CREB pathways at spinal (Ji et al 2002) and supra-spinal sites (Di Benedetto et al 2011). In the DRG, we observed a persistent up-regulation of pERK and c-Fos in all experimental conditions (from 30 min to 7-14 days after manipulation).…”

Section: Discussionmentioning

confidence: 99%

Effects of surgery and/or remifentanil administration on the expression of pERK1/2, c-Fos and dynorphin in the dorsal root ganglia in mice

Romero

González-Cuello

Laorden

et al. 2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Tissue injury and/or opioids induce plastic changes in the spinal cord resulting in pain hypersensitivity; the contribution of the dorsal root ganglia (DRG) is poorly understood. We evaluated DRG phenotypic changes induced by surgery and/or remifentanil in a mice model of postoperative pain using as neuronal markers ERK1/2 and c-Fos; prodynorphin mRNA and dynorphin levels were also determined. We hypothesized that a correlation between nociception and DRG reactivity would occur. Surgery and/or remifentanil induced mechanical hypersensitivity, correlated with ERK1/2 phosphorylation and c-Fos expression in the DRG; changes were greater in the remifentanil + incision group and still present on day 14 (p < 0.01 vs. control). Intrathecal PD98059 (ERK1/2 inhibitor) partially reversed the mechanical hypersensitivity (44%, p < 0.05) observed in the remifentanil + incision group. In this group, significant increases in prodynorphin mRNA (at 2, 7, and 14 days, p < 0.01) roughly coincided with increases in dynorphin (days 2 and 14, p < 0.001) in the DRG. Remifentanil or incision (alone) also induced an up-regulation in prodynorphin mRNA expression on days 7 and 14 (p < 0.01, p < 0.05, respectively), partially correlating with dynorphin levels. On day 21, all molecular changes returned to control levels in all experimental conditions, concurring with the complete recovery of nociceptive thresholds. Surgery and/or remifentanil induce up-regulation of c-Fos and pERK in the DRG, approximately correlating with nociceptive behavior, also associated with an increased expression of prodynorphin/dynorphin. These changes support the role of the DRG in the development and maintenance of pain hypersensitivity after surgery. The findings could contribute to the development of new therapeutic agents focused on peripheral targets.

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Regulation of opioid gene expression in the rat brainstem by 3,4-methylenedioxymethamphetamine (MDMA): role of serotonin and involvement of CREB and ERK cascade

Cited by 13 publications

References 67 publications

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

Sex-Dependent Psychoneuroendocrine Effects of THC and MDMA in an Animal Model of Adolescent Drug Consumption

Discriminative Stimulus Effects of Hallucinogenic Drugs: a Possible Relation to Reinforcing and Aversive Effects

Effects of surgery and/or remifentanil administration on the expression of pERK1/2, c-Fos and dynorphin in the dorsal root ganglia in mice

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