Abstract Ethanol and 3, 4‐Methylenedioxymethamphetamine ( MDMA ) are popular recreational drugs widely abused by adolescents that may induce neurotoxic processes associated with behavioural alterations. Adolescent CD 1 mice were subjected to ethanol intake using the drinking in the dark ( DID ) procedure, acute MDMA or a combination. Considering that both drugs of abuse cause oxidative stress...
Abstract Evidence is accumulating to suggest that 3,4‐methylenedioxymethamphetamine ( MDMA ) has neurotoxic and neuroinflammatory properties. MDMA is composed of two enantiomers with different biological activities. In this study, we evaluated the in vivo effects of S(+)‐ MDMA , R(−)‐ MDMA , and S(+)‐ MDMA in combination with R(−)‐ MDMA on microglial and astroglial activation compared with...
To characterize the long-term effects of adolescent marijuana abuse, we performed a proteomic analysis of cerebellar extracts from adult female rats with and without ovariectomy that were treated with Δ9-THC for 40 days during adolescence. Six proteins were found to significantly differ among the four treatment groups, with Δ9-THC and ovariectomy (OVX) decreasing the mitochondrial proteins,...
Chronic use of marijuana impairs synaptic plasticity and cognitive function. However, the molecular mechanisms by which marijuana alters long-term synaptic plasticity are largely unknown. Here, we show that repeated in vivo exposures to Delta9-THC for 7 consecutive days significantly impaired hippocampal long-term potentiation (LTP) of excitatory glutamatergic synaptic transmission. The...
J. Neurochem. (2010) 10.1111/j.1471‐4159.2010.06578.x Abstract 3,4‐Methylenedioxymethamphetamine (MDMA, ‘ecstasy’) produces selective long‐lasting serotonergic neurotoxicity in rats. The drug also produces acute hyperthermia which modulates the severity of the neurotoxic response. In addition, MDMA produces signs of neuroinflammation reflected as microglial activation and an increase in the...
J. Neurochem. (2009) 112 , 951–962. Abstract 3,4‐Methylenedioxymethamphetamine (MDMA; ‘Ecstasy’) is a popular recreational drug used worldwide. This study aimed to determine the effects of this compound on the expression of nerve terminal serotonergic markers in rats. Experiment 1 investigated MDMA‐induced changes in levels of the serotonin transporter (SERT) and the vesicular monoamine...
Early postnatal blockade of NMDA receptors by phencyclidine (PCP) causes cortical apoptosis in animals. This is associated with the development of schizophrenia-like behaviors in rats later in life. Recent studies show that the mechanism involves a loss of neurotrophic support from the phosphoinositol-3 kinase/Akt pathway, which is normally maintained by synaptic NMDA receptor activation. Here...
Phosphodiesterase 5 (PDE5) inhibitors are often used in combination with club drugs such as 3,4-methylenedioxymethamphetamine (MDMA or ecstasy). We investigated the consequences of such combination in the serotonergic system of the rat. Oral administration of sildenafil citrate (1.5 or 8 mg/kg) increased brain cGMP levels and protected in a dose-dependent manner against 5-hydroxytryptamine...
Abstract Acute administration of repeated doses of 3,4‐methylenedioxymethamphetamine (MDMA, ecstasy) dramatically reduces striatal dopamine (DA) content, tyrosine hydroxylase (TH), and DA transporter‐immunoreactivity in mice. In this study, we show for the first time the spatiotemporal pattern of dopaminergic damage and related molecular events produced by MDMA administration in mice. Our...
Several lines of evidence suggest the involvement of the raphe-serotonergic neurons in addiction to psychostimulants and some recreational drugs. In this study, we established rat organotypic mesencephalic slice cultures containing the raphe nuclei and examined the effects of sustained exposure to 3,4-methylenedioxymethamphetamine (MDMA) and methamphetamine (METH). Immunostaining for tryptophan...
Although cannabinoid-induced behavioral sensitization and cross-sensitization with opiates has been recently demonstrated, no information is available on the associated state and responsiveness of dopamine (DA) transmission in the nucleus accumbens (NAc) shell and core. In this study we investigate by means of dual probe microdialysis, the effect of exposure to a sensitizing regimen of...
The psychoactive ingredient of marijuana, Delta9-tetrahydrocannabinol (Delta9-THC), can evoke apoptosis in cultured cortical neurones. Whilst the intracellular mechanisms responsible for this apoptotic pathway remain to be fully elucidated, we have recently identified a role for the CB1 type of cannabinoid (CB) receptor and the tumour suppressor protein, p53. In the current study, we...
Abstract R,S(±)‐3,4‐methylenedioxymethamphetamine (R,S(±)‐MDMA, ‘Ecstasy’) is known to stimulate dopamine (DA) transmission in the nucleus accumbens (NAc). In order to investigate the post‐synaptic correlates of pre‐synaptic changes in DA transmission and their relationship with MDMA enantiomers, we studied the effects of R,S(±)‐MDMA, S(+)‐MDMA, and R(−)‐MDMA on extracellular DA and...
Brain-derived neurotrophic factor (BDNF) is involved in synaptic development and plasticity, and alterations in BDNF expression or signaling are implicated in drug addiction and psychiatric diseases, such as depression and schizophrenia. In this study, we administered phencyclidine to postnatal and adult rats with different time schedules, and determined the correlations between BDNF expression...
To date, several studies have demonstrated that phospholipase C-coupled receptors stimulate the production of endocannabinoids, particularly 2-arachidonoylglycerol. There is now evidence that endocannabinoids are involved in phospholipase C-coupled serotonin 5-HT(2A) receptor-mediated behavioral effects in both rats and mice. The main objective of this study was to determine whether activation...
Abstract: Psychotic disorders affecting up to 1% of the human population represent pathological changes to the metabolic homeostasis of the brain. Increasing evidence in the literature suggests complex biochemical and/or transcriptional alterations accompanying schizophrenia‐like phenomena. Sub‐chronic treatment with sub‐anaesthetic doses of ketamine induces schizophrenia‐related psychotic...
Experiments compared a series of phenethylamine hallucinogens with their phenylisopropylamine analogues for binding affinity and ability to stimulate serotonin 5-HT 2A receptor-mediated hydrolysis of phosphatidyl inositol in cells expressing cloned rat and human 5-HT 2A receptors. The (+/-)phenylisopropylamine analogues had significantly higher intrinsic activities for 5-HT 2A receptor-mediated...
Abstract 3,4,‐Methylenedioxymethamphetamine (MDMA; ‘ecstasy’) acts at monoamine nerve terminals to alter the release and re‐uptake of dopamine and 5‐HT. The present study used microdialysis in awake rats to measure MDMA‐induced changes in extracellular GABA in the ventral tegmental area (VTA), simultaneous with measures of extracellular dopamine (DA) in the nucleus accumbens (NAC) shell....
We recently demonstrated that the potent hallucinogenic drug lysergic acid diethylamide (LSD) dynamically influences the expression of a small collection of genes within the mammalian prefrontal cortex. Towards generating a greater understanding of the molecular genetic effects of hallucinogens and how they may relate to alterations in behavior, we have identified and characterized expression...
Abstract: Neurotoxicity induced by different substituted amphetamines has been associated with the exhaustion of intracellular energy stores. Accordingly, we examined the influence of 2‐deoxy‐D‐glucose (2‐DG), a competitive inhibitor of glucose uptake and metabolism, and nicotinamide, an agent that improves energy metabolism, on 3,4‐methylenedioxymethamphetamine (MDMA)‐induced...
Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide...
Several amphetamine analogues are reported to increase striatal glutamate efflux in vivo, whereas other data indicate that glutamate is capable of stimulating the efflux of dopamine (DA) in the striatum via a glutamate receptor-dependent mechanism. Based on these findings, it has been proposed that the ability of glutamate receptor-blocking drugs to antagonize the effects of amphetamine may be...
Abstract: In vivo microdialysis was used to determine whether the 3,4‐methylenedioxymethamphetamine (MDMA)‐induced release of serotonin (5‐HT) in vivo involves a carrier‐mediated process and to investigate further the state‐dependent interaction between 5‐HT and dopamine. MDMA produced a dose‐dependent increase in the extracellular concentration of 5‐HT in the striatum and prefrontal cortex...
5-Hydroxytryptamine2 (5-HT2) receptor antagonists have been shown to interfere with the stimulation of striatal dopamine synthesis and release produced by the amphetamine analogue 3,4-methylenedioxymethamphetamine (MDMA). To localize the receptors responsible for the attenuation of MDMA-induced release, 5-HT2 receptor antagonists were infused via the microdialysis probe directly into the brains...