Is recreational ecstasy (MDMA) use associated with higher levels of depressive symptoms?

Due to potential serotonergic deficits, 3,4-methylenedioxymethamphetamine (MDMA or Ecstasy) may cause long-term mood disruptions in recreational Ecstasy users. The purpose of this review is to evaluate the evidence for a relationship between recreational Ecstasy use and higher levels of depressive symptoms. Eleven out of 22 studies initially have reported significantly higher depression scores in Ecstasy users in comparison to control participants. However, only three studies ultimately have revealed significantly higher depression scores in comparison to cannabis or polydrug controls. Furthermore, most studies have suffered from methodological weaknesses, and the levels of depressive symptoms that have been found in Ecstasy users have not been shown to be much higher than those found in normative groups. The evidence for an association specifically between Ecstasy use and higher levels of depressive symptoms is currently unconvincing, but the frequent concomitant use of Ecstasy and other illicit drugs has been shown to be associated with higher levels of depressive symptoms. Possible causes include polydrug use in general, MDMA-induced serotonergic deficits, individual effects of illicit drugs besides Ecstasy, combined effects of MDMA and other illicit drugs, and preexisting differences in the levels of depressive symptoms in Ecstasy users.     

Effects of synthetic (-)-huperzine A on cholinesterase activities and mouse water maze performance

目的：比较合成和天然左旋石杉碱甲（ＨｕｐＡ）对胆碱酯酶的抑制作用以及对东莨菪碱所致记忆障碍的改善作用．方法：比色法用于测定胆碱酯酶活性，小鼠水迷宫用于评价促智作用．结果：合成ＨｕｐＡ抑制大鼠皮层和红细胞膜乙酰胆碱酯酶的ＩＣ５０值分别为６４７（５２６－７９５），５３９（４３６－６６６）ｎｍｏｌ·Ｌ－１，抑制大鼠血清丁酰胆碱酯酶的ＩＣ５０为５３６（４４９－６３８）μｍｏｌ·Ｌ－１．灌服合成ＨｕｐＡ（０１２－０４８ｍｇ·ｋｇ－１），量效依赖性抑制小鼠体内的胆碱酯酶．行为实验证明，合成ＨｕｐＡ（００５ｍｇ·ｋｇ－１）明显地改善东莨菪碱所致的记忆损害．合成ＨｕｐＡ具有与天然ＨｕｐＡ相等的效力．结论：合成ＨｕｐＡ与天然ＨｕｐＡ具有相似的药理活性．     

Residual effects of zopiclone 7.5 mg on highway driving performance in insomnia patients and healthy controls: a placebo controlled crossover study

Rationale

Residual effects of hypnotics on driving performance have been mainly determined in studies using a standardized driving test with healthy good sleepers. Responses to effects may differ, however, between insomniacs and healthy volunteers due to the underlying sleep disorder. In addition, a majority of insomniacs uses hypnotics chronically resulting in the development of tolerance to impairing effects. Impaired driving performance in healthy volunteers may then be an overestimation of the actual effects in insomniacs.

Objectives

The present study aims to compare the residual effects of zopiclone 7.5 mg on on-the-road driving performance of 16 middle-aged insomniacs chronically using hypnotics (chronic users), 16 middle-aged insomniacs not or infrequently using hypnotics (infrequent users), and 16 healthy, age matched, good sleepers (controls).

Methods

The study was conducted according to a 3?×?2 double-blind, placebo controlled crossover design, with three groups and two treatment conditions. Treatments were single oral doses of zopiclone 7.5 mg and placebo administered at bedtime (2330 hours). Between 10 and 11 h after administration subjects performed a standardized highway driving test.

Results

Zopiclone 7.5 mg significantly impaired on-the-road driving performance in both insomnia groups and healthy controls. The magnitude of impairment was significantly less in the chronic users group as compared with the controls.

Conclusions

The smaller magnitude of effects suggests that investigating residual effects of hypnotics in healthy volunteers may yield a minor overestimation of the actual effects in insomnia patients.     

Distinct periods of developmental sensitivity to the effects of 3,4-(±)-methylenedioxymethamphetamine (MDMA) on behaviour and monoamines in rats

Previous findings showed allocentric and egocentric learning deficits in rats after MDMA treatment from postnatal days (PD) 11-20 but not after treatment from PD 1-10. Shorter treatment periods (PD 1-5, 6-10, 11-15, or 16-20) resulted in allocentric learning deficits averaged across intervals but not for any interval individually and no egocentric learning deficits individually or collectively. Whether this difference was attributable to treatment length or age at the start of treatment was unclear. In the present experiment rat litters were treated on PD 1-10, 6-15, or 11-20 with 0, 10, or 15 mg/kg MDMA q.i.d. at 2-h intervals. Two male/female pairs/litter received each treatment. One pair/litter received acoustic startle with prepulse inhibition, straight channel swimming, Cincinnati water maze (CWM), and conditioned fear in a latent inhibition paradigm. The other pair/litter received locomotor activity, straight channel swimming, Morris water maze (MWM), and locomotor activity retest with MK-801 challenge. MDMA impaired CWM learning following PD 6-15 or 11-20 exposure. In MWM acquisition, all MDMA-treated groups showed impairment. During reversal and shift, the PD 6-15 and PD 11-20 MDMA-treated groups were significantly impaired. Reductions in locomotor activity were most evident after PD 6-15 treatment while increases in acoustic startle were most evident after PD 1-10 treatment. After MK-801 challenge, MDMA-treated offspring showed less locomotion compared to controls. Region-specific changes in brain monoamines were also observed but were not significantly correlated with behavioural changes. The results show that PD 11-20 exposure to MDMA caused the largest long-term cognitive deficits followed by PD 6-15 exposure with PD 1-10 exposure least affected. Other effects, such as those upon MK-801-stimulated locomotion showed greatest effects after PD 1-10 MDMA exposure. Hence, each effect has a different window of developmental susceptibility.     

Effect of ambient temperature and a prior neurotoxic dose of 3,4-methylenedioxymethamphetamine (MDMA) on the hyperthermic response of rats to a single or repeated (‘binge’ ingestion) low dose of MDMA

Rationale 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) administration to rats produces acute hyperthermia and long-term neurotoxic damage to 5-hydroxytryptamine (serotonin, 5-HT) neurones.Objective We wished to examine MDMA-induced hyperthermia in rats housed at normal (19°C) and high (30°C) room temperatures and investigate the effect of a prior neurotoxic lesion.Methods Rectal temperature was measured after administration of single or repeated doses of MDMA to rats housed at 19°C and 30°C.Results MDMA (5 mg/kg IP) produced a sustained hyperthermic response in rats housed at 30°C, but not in rats housed at 19°C. A prior (5 weeks earlier) neurotoxic dose of MDMA (12.5 mg/kg IP) resulted in MDMA (5 mg/kg) producing a greater hyperthermic response in rats housed at 30°C than in non-pre-treated animals. Repeated MDMA administration (binge dosing; 2, 4 or 6 mg/kg ×3) produced dose-dependent hyperthermia in rats housed at 19°C, with MDMA (2 mg/kg ×3) having little effect. However, this dose produced significant hyperthermia (2°C above control values)in rats housed at 30°C following the third dose. A prior neurotoxic dose of MDMA resulted in MDMA (2 mg/kg ×3) producing marked hyperthermia (>1°C) after the first dose and severe hyperthermia (2°C) after the third dose.Conclusions MDMA administration to rats housed at 30°C produces a more severe hyperthermic response than that seen in rats housed at 19°C. A prior neurotoxic dose enhances the response further in animals housed at 30°C. Binge dosing produces a higher final peak response than a similar non-divided dose. This effect is more marked in animals housed at high room temperature. These data may have implications for recreational users of MDMA in hot environments, particularly those who may have damaged serotoninergic neurones because of prior heavy or frequent use of the drug.     

Positron emission tomographic studies of brain dopamine and serotonin transporters in abstinent (±)3,4-methylenedioxymethamphetamine (“ecstasy”) users: relationship to cognitive performance

BACKGROUND: (+/-)3,4-Methylenedioxymethamphetamine (MDMA, "ecstasy") is a recreational drug and brain serotonin (5-HT) neurotoxin. Under certain conditions, MDMA can also damage brain dopamine (DA) neurons, at least in rodents. Human MDMA users have been found to have reduced brain 5-HT transporter (SERT) density and cognitive deficits, although it is not known whether these are related. This study sought to determine whether MDMA users who take closely spaced sequential doses, which engender high plasma MDMA concentrations, develop DA transporter (DAT) deficits, in addition to SERT deficits, and whether there is a relationship between transporter binding and cognitive performance. MATERIALS AND METHODS: Sixteen abstinent MDMA users with a history of using sequential MDMA doses (two or more doses over a 3- to 12-h period) and 16 age-, gender-, and education-matched controls participated. Subjects underwent positron emission tomography with the DAT and SERT radioligands, [(11)C]WIN 35,428 and [(11)C]DASB, respectively. Subjects also underwent formal neuropsychiatric testing. RESULTS: MDMA users had reductions in SERT binding in multiple brain regions but no reductions in striatal DAT binding. Memory performance in the aggregate subject population was correlated with SERT binding in the dorsolateral prefrontal cortex, orbitofrontal cortex, and parietal cortex, brain regions implicated in memory function. Prior exposure to MDMA significantly diminished the strength of this relationship. CONCLUSIONS: Use of sequential MDMA doses is associated with lasting decreases in brain SERT, but not DAT. Memory performance is associated with SERT binding in brain regions involved in memory function. Prior MDMA exposure appears to disrupt this relationship. These data are the first to directly relate memory performance to brain SERT density.     

Effects of morphine and methadone treatment on mRNA expression of Gα(i) subunits in rat brains

Methadone is clinically effective as substitution therapy in patients with opioid dependence. The diversity of methadone and morphine in their intracellular activity is postulated. We compared the effects of repeated daily treatment of Sprague-Dawley rats with morphine (10 mg/kg) and methadone (1 mg/kg) on the expression of the Gα(i1-i3) mRNAs in several rat brain areas using RT-qPCR. We found that both opioid receptor agonists decreased Gα(i3) mRNA in only the nucleus accumbens. Although there was no difference in the influence of morphine and methadone on Gα(i), our results indicate that among Gα(i) subunits, the Gα(i3) is specifically involved in the mechanism of action of both drugs.     

Effects of Simultaneous Administration of Tributyltin (TBT) and p,p ′ -DDE on Female Offspring of Wistar Rats

p,p ' -DDE (DDE) and tributyltin (TBT) occur globally and in Japan were shown to bioaccumulate in marine products, thus serving as a source of contamination in the mammalian food chain. Consequently, fetuses and neonates, through maternal ingestion, may be exposed to DDE and TBT. Therefore, the effects of combined DDE and TBT were investigated in female Wistar rat offspring of dams ingesting these two contaminants. In this study, TBT suppressed the growth of female offspring and delayed eye opening. However, both growth retardation and delayed eye opening produced by TBT failed to occur in the presence of DDE. These results indicated that TBT or DDE affected the development of female rat offspring following maternal exposure and simultaneous administration of DDE prevented some of the observed effects of TBT through a mechanism that remains to be elucidated.     

The Effects of Etimicin and Gentamicin on Renal Endoplasmic Reticulum ~(45)Ca~(2 )-Uptake and Ca~(2 )-Mg~(2 )-ATPase Activity

目的：研究爱大霉素和庆大霉素对大鼠肾皮质内质网４５Ｃａ２＋摄取以及对内质网膜上Ｃａ２＋Ｍｇ２＋ＡＴＰａｓｅ活性的影响。方法：４５Ｃａ２＋示踪技术和孔雀蓝分光光度法。结果：爱大霉素和庆大霉素在大于或等于３．４×１０４ｍｏｌ·Ｌ１时，能抑制内质网４５Ｃａ２＋摄取（抑制率分别大于或等于１７．４％和２５．５％）；在３．４×１０２ｍｏｌ·Ｌ１时，对内质网膜上Ｃａ２＋Ｍｇ２＋ＡＴＰａｓｅ活性有抑制作用（抑制率分别为２４．１７％和２９．１９％）。结论：爱大霉素和庆大霉素在较高浓度时可使胞浆钙升高，这可能与其产生肾毒性有关     

Effects of pentachlorophenol and dichlorodiphenyltrichloroethane on secretion of interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) from human immune cells

Pentachlorophenol (PCP) and dichlorodiphenyltrichloroethane (DDT) are pesticides that have been widely used and significantly contaminate the environment. Both are found in human blood and have been shown to alter the lytic and binding function of human natural killer (NK) cells. Interferon gamma (IFNγ) and tumor necrosis factor alpha (TNFα) are pro-inflammatory cytokines, which regulate immune responsiveness to pathogens and tumors. Their levels require very tight control to prevent loss of immune competence or excessive inflammation. Here, we examined the capacity of PCP and DDT to alter the secretion of these critical pro-inflammatory cytokines from increasingly reconstituted (more complex) preparations of human immune cells which included NK cells, monocyte-depleted (MD) peripheral blood mononuclear cells (PBMCs) (a preparation that is predominantly lymphocytes) and PBMCs (a preparation containing lymphocytes and monocytes). Results indicated that exposure to PCP decreased IFNγ secretion at the highest exposures (2.5 and 5?μM) and increased IFNγ secretion at lower concentrations. These effects were seen irrespective of the complexity of the cell preparation. PCP at 2.5 and 5?μM generally decreased TNFα secretion from NK cells, but had inconsistent effects in MD-PBMCs and PBMCs. Exposure of each of the immune cell preparations to DDT caused increase in IFNγ secretion. DDT (2.5?μM) increased TNFα secretion from MD-PBMCs after either 24?h or 48?h of exposure. The mechanism of PCP-induced increase in IFNγ secretion appears to involve the p38 mitogen activated protein kinase (MAPK) pathway, based on loss of PCP stimulated increase when this pathway was inhibited.     

Effects of intraplantar nocistatin and (±)-J 113397 injections on nociceptive behavior in a rat model of inflammation

Nocistatin (NST) and Nociceptin/Orphanin FQ (N/OFQ) are derived from the same precursor protein, pre-proN/OFQ, and exert opposite effects on the modulation of pain signals. However, the role of the peripheral N/OFQ and the NOP receptor, which is located at the endings of sensory nerves, in inflammatory pain was not ascertained. NST administered intrathecally (i.t.) prevented the nociceptive effects induced by i.t. N/OFQ and PGE₂. Moreover an up regulation of N/OFQ was shown in the rat in response to peripheral inflammation. Here, we investigated the effects of intraplantar (i.pl.) administration of functional N/OFQ and NOP receptor antagonists in a rat model of inflammatory pain. Our findings showed that i.pl. injection of (±)-J 113397, a selective antagonist of the NOP receptor, and NST, the functional N/OFQ antagonist, prior to carrageenan significantly reduced the paw allodynic and thermal hyperalgesic threshold induced by the inflammatory agent. The resulting antiallodynic and antihyperalgesic effects by co-administering NST and (±)-J 113397 prior to carrageenan were markedly enhanced, and the basal latencies were restored. Thus, it is likely that the peripheral N/OFQ/NOP receptor system contributes to the abnormal pain sensitivity in an inflammatory state.     

Effects of sazetidine-A, a selective α4β2 nicotinic acetylcholine receptor desensitizing agent on alcohol and nicotine self-administration in selectively bred alcohol-preferring (P) rats

Rationale

Manipulations of nicotinic cholinergic receptors have been shown to influence both alcohol and nicotine intake. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] is a novel compound that potently and selectively desensitizes α4β2 nicotinic receptors with only modest receptor activation.

Objectives

The goal of the present study was to examine the effects of sazetidine-A on alcohol and nicotine self-administration in alcohol-preferring (P) rats.

Methods

P rats were given the choice of water or alcohol. Once stable baselines were established, the acute (0, 0.1, 0.3, 1, and 3 mg/kg, s.c.) and chronic (3 mg/kg for 10 days) effects of sazetidine-A on alcohol intake were assessed. Naltrexone (2.5 mg/kg) served as a positive control. The effect of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on saccharin (0.2%) preference was also assessed. In addition, the acute effects of sazetidine-A (3 mg/kg) and naltrexone (4 mg/kg) on alcohol intake after alcohol deprivation were evaluated. In another experiment, the effects of sazetidine-A (0, 1, or 3 mg/kg) on IV nicotine self-administration in P and NP rats were assessed.

Results

Sazetidine-A caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake until the seventh day of treatment, when partial tolerance appeared to develop. In the post-deprivation study, sazetidine-A significantly reduced alcohol intake and preference. Sazetidine-A at 3 mg/kg significantly reduced nicotine self-administration in both lines.

Conclusions

Sazetidine-A significantly reduced alcohol and nicotine intake in P rats that self-administer higher levels of both drugs. Sazetidine-A may hold promise for the treatment of alcohol and nicotine addiction.     

12-week double-blind randomized multicenter study of efficacy and safety of agomelatine (25–50 mg/day) versus escitalopram (10–20 mg/day) in out-patients with severe generalized anxiety disorder

Treatment of severely symptomatic patients with generalized anxiety disorder (GAD) raises particular concerns for clinicians.This 12-week double-blind study evaluated the efficacy of agomelatine (25–50?mg/day) in the treatment of patients with severe GAD, using escitalopram (10–20?mg) as active comparator. The primary outcome measure was the change from baseline of the total score on the Hamilton Anxiety scale (HAM-A) at week 12. Secondary outcome measures included rate of response to treatment (at least 50% score reduction from baseline) in the HAM-A psychic and somatic anxiety sub-scores, Clinical Global Impression severity and change scores, the Toronto Hospital Alertness Test, the Snaith-Hamilton Pleasure Scale, and the Leeds Sleep Evaluation Questionnaire Scores.Sixty one clinical centers (Australia, Canada, Czech Republic, Finland, Germany, Hungary, Poland, Russia, Slovakia) participated from April 2013 to February 2015.Patient characteristics and demographic data were comparable between treatment groups. Both treatments were associated with a clinically significant decrease in HAM-A total score at week 12; the non-inferiority of agomelatine versus escitalopram was not demonstrated (E(SE)?=??0.91(0.69), 95%CI?=?[?2.26, 0.44], p?=?0.195). At week 12, the response rate was 60.9% in the agomelatine group, and 64.8% in the escitalopram group. In both treatment arms, HAM-A psychic and somatic anxiety scores decreased, alertness and sleep parameters improved, and ability to experience pleasure increased. In these secondary outcome measures, there were no significant differences between the treatment groups. Agomelatine was well-tolerated, with a lower incidence of adverse events than escitalopram.Agomelatine and escitalopram are efficacious in treating GAD patients with severe symptoms.     

Effects of (+)- and (±)-sotalol on repolarizing outward currents and pacemaker current in sheep cardiac Purkinje fibres

Summary This study was aimed to differentiate the action of (+)- and (±)-sotalol (10–1000 mol/l) on membrane currents which are active during the repolarization of cardiac action potentials Effects where studied in shortened sheep cardiac Purkinje fibres with the two-microelectrode voltage-clamp technique Action potentials were activated at a frequency of 0.25 Hz and membrane currents at 0.03 Hz or 0.05 Hz in most experiments.Out of the currents investigated the transient outward current (i_to) reacted most sensitively to (+)- and (±)-sotalol. I_to-amplitude was decreased on the average to 77% of reference at 10 mol/l and to 53% at 1000 mol/l (+)- or (±)-sotalol. The maximally available ito-current was decreased but the voltage-dependent control of inactivation was left nearly unchanged. The initial inwardly rectifying current (i_Ki), which propels the last repolarization phase of the action potential and controls resting potential to a large extent was reduced on the average to 93% of reference at 10 mol/l and to 62% at 1000 mol/l (+)- or (±)-sotalol. Time-dependent (delayed) outward current (i_K) was on the average not affected by (+)- or (±)-sotalol up to 100 mol/l and was decreased to 84% of reference current under the influence of 1000 mol/l. An initial outward current, which is activated at positive membrane potentials (i_inst) was not clearly affected by (+)- or (±)-sotalol at concentrations up to 1000 mol/l Pacemaker current (i_f) was not influenced by the drugs up to 100 mol/l. Only at 1000 mol/l was the amount of available i_f-current decreased to 79% of reference. (The potential-dependent control of activation was not affected) Time constants of time-dependent currents i_to, i_K and i_f did not change in concentrations up to 1000 mol/l of the drug.Action potential duration increased at (+)- or (±)-sotalol concentrations 10 mol/l and maximal prolongation was achieved at concentrations of 100–300 mol/l Resting potential remained nearly unchanged at these concentrations, but the membranes depolarized at 1000 mol/l. According to our data action potential prolongation in sheep Purkinje fibres under the influence of (+)- and (±)-sotalol correlates to the drug-induced block to i_to-current and inwardly rectifying i_K1-current.Supported by the Deutsche Forschungsgemeinschaft SFB 242, C 1 Send offprint requests to U. Borchard at the above address     

Effects of oxaprozin and of other 2-arylpropionic acid derivatives on nuclear factor κB(NF-κB) activation

The translocation to the nucleus and the binding of NF-B to DNA is thought to play a fundamental role in the activation of immune and inflammatory cells in order to activate the genes that in turn produce cytokines. We evaluated the ability of some 2-arylpropionic acid derivatives (fenoprofen, flurbiprofen, ketoprofen, S- and R-isomers of ibuprofen, ibuprofen, naproxen, and oxaprozin) to affect NF-B binding to DNA in human peripheral mononuclear cells. We observed NF-B inhibition by oxaprozin (IC₅₀ = 50 M), ibuprofen (185 M) and S-ibuprofen (51 M). Since oxaprozin reaches higher concentrations in synovial tissues and fluid (4—5 times higher than in plasma, i.e. around 100 M) its inhibitory activity is clinically relevant. The inhibitory activity observed with all other tested drugs was outside their clinically relevant concentrations. At the concentrations observed to affect the NF-B binding, oxaprozin and ibuprofen also inhibited the release of TNF- and interleukin 1 in cells stimulated by Escherichia coli lipolysaccharide. By administering oxaprozin or ibuprofen at high dosage it should be possible to inhibit NF-B DNA binding in humans in vivo.     

Effects of bis(2-ethylhexyl) phthalate, γ-hexachlorocyclohexane, and 17β-estradiol on the fry stage of medaka (Oryzias latipes)

The effects of bis(2-ethylhexyl) phthalate (DEHP), γ-hexachlorocyclohexane (γ-HCH), and 17β-estradiol (E2) on the fry stage of medaka were investigated. The medaka fry were exposed to different concentrations (0.01, 0.1, 1, and 10μg/L) of these chemicals for 3 weeks after hatching. Then, mortality, body weight, sex ratio, and gonadosomatic index (GSI) of the matured fish (after 5 months) were measured. Mortality was increased significantly in the 10μg/L E2 group. Distortion of sex ratio was found in 1 and 10μg/L E2 groups. DEHP treated groups showed the GSI reduction only in male fish. All the γ-HCH and parts of the E2 treated groups showed the GSI reduction in both sexes. Exposure of DEHP, γ-HCH, and E2 during the fry stage affected normal maturation of medaka at the concentrations which had no impact on mortality or sex ratio.     

A study of the neurotoxic effect of MDMA (‘ecstasy') on 5-HT neurones in the brains of mothers and neonates following administration of the drug during pregnancy

1. It is well established that 3,4-methylenedioxymethamphetamine (MDMA or ‘ecstasy'') is neurotoxic and produces long term degeneration of cerebral 5-hydroxytryptamine (5-HT) nerve terminals in many species. Since MDMA is used extensively as a recreational drug by young people, it is being ingested by many women of child bearing age. We have therefore examined the effect of administering high doses of MDMA to rats during pregnancy on the cerebral content of both the dams and the neonates.
2. MDMA (20 mg kg⁻¹, s.c.) was injected twice daily on days 14–17 of the gestation period. The initial dose produced a marked hyperthermic response in the dam which was progressively attenuated in both peak height and area under the curve following further doses of the drug. The body weight of the dams decreased during the period of treatment.
3. There was a modest decrease in litter size (−20%) of the MDMA-treated dams.
4. The concentration of 5-HT and its metabolite 5-HIAA was decreased by over 65% in the hippocampus and striatum and 40% in the cortex of the dams 1 week after parturition. In contrast, the content of 5-HT and 5-HIAA in the dorsal telencephalon of the pups of the MDMA-treated dams was the same as that seen in tissue from pups born to control animals.
5. Administration of MDMA (40 mg kg⁻¹, s.c.) to adult rats increased thiobarbituric acid reacting substances (TBARS) in cortical tissue 3 h and 6 h later, indicating increased lipid peroxidation. No increase in TBARS was seen in the cortical tissue of 7–10 day neonates injected with this dose of MDMA 3 h or 6 h earlier.
6. The data suggest that exposure to MDMA in utero during the maturation phase does not produce damage to 5-HT nerve terminals in the foetal rat brain, in contrast to the damage seen in the brains of the mothers. This may be due to MDMA being metabolized to free radical producing entities in the adult brain but not in the immature brain or, alternatively, to more effective or more active free radical scavenging mechanisms being present in the immature brain.