Blockade of nitric oxide signalling promotes resilience to the effects of social defeat stress on the conditioned rewarding properties of MDMA in mice.

MDMA abuse continues being a serious problem in our society. Environmental factors, such as stress, increase the vulnerability of individuals to develop drug abuse and we have observed that exposure to social defeat (SD) stress alters the sensitivity of mice to the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. In the present study, we evaluated the role of the nitric oxide (NO) pathway in the effects of SD on the rewarding properties of MDMA. Three groups of mice were treated with an inhibitor of NO synthesis, 7-nitroindazole (0, 7.25 and 12.5 mg/kg), before each exposure to SD and place conditioning with MDMA (1.25 mg/kg) on PND 54, 56, 58, and 60. One control group was not exposed to SD before place conditioning. In addition, we studied the effects of SD on the levels of nitrites in the striatum, hippocampus and frontal cortex. Our results showed that the low dose of 7-nitroindazole blocked the effects of SD on the rewarding properties of MDMA. Moreover, SD exposure increased the nitrites in the prefrontal cortex and hippocampus. These results demonstrated the role of NO signalling in the effects of SD stress in mice and suggested that the inhibition of NO synthesis may confer resilience to the effects of social stress on the rewarding properties of MDMA. The manipulation of the NO signalling pathway could be a useful target for the treatment of MDMA-dependent subjects who experienced high levels of stress.

Role of NMDA and AMPA glutamatergic receptors in the effects of social defeat on the rewarding properties of MDMA in mice.

Exposure to social stress alters the response to drugs of abuse of experimental animals. Changes in the glutamatergic system seem to play a role in the effects of social defeat stress on the rewarding properties of cocaine and amphetamine. The aim of the present study was to evaluate the involvement of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the effects of social defeat on the conditioned place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our hypothesis was that changes in these receptors could mediate the effects of social defeat on MDMA reward. Young adult male mice were exposed to an episode of social defeat with an aggressive conspecific immediately before each conditioning session with MDMA (1.25 mg/kg, four sessions on alternating days). According to the treatment received before defeats, six groups were used: saline, 5 or 10 mg/kg of memantine (NMDA antagonist) and 0.25, 1 or 5 mg/kg of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA antagonist). One control group was exposed to exploration before place conditioning. In two additional defeated and control groups, the membrane expression of NMDA and AMPA receptors was determined in the striatum and the hippocampus. Control and memantine-treated groups developed place preference, but not defeated mice treated with saline or CNQX, suggesting that the blockade of NMDA receptors reversed the effects of social defeat. Social defeat decreased the expression of several subunits of NMDA and AMPA receptors, mainly GluN1 and GluA1. These results demonstrated that glutamatergic plasticity is involved in the effects of social defeat stress on MDMA reward.

Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait.

Adolescent exposure to cannabinoids enhances the behavioural effects of cocaine, and high novelty-seeking trait predicts greater sensitivity to the conditioned place preference (CPP) induced by this drug. Our aim was to evaluate the influence of novelty-seeking on the effects of adolescent cannabinoid exposure. Adolescent male mice were classified as high or low novelty seekers (HNS and LNS) in the hole-board test. First, we evaluated the CPP induced by the cannabinoid agonist WIN 55212-2 (0.05 and 0.075 mg/kg, i.p.) in HNS and LNS mice. Then, HNS and LNS mice were pretreated i.p. with vehicle, WIN 55212-2 (0.1 mg/kg), or cannabinoid antagonist rimonabant (1 mg/kg) and were subsequently conditioned with WIN 55212-2 (0.05 mg/kg, i.p.) or cocaine (1 or 6 mg/kg, i.p.). Only HNS mice conditioned with the 0.075 mg/kg dose acquired CPP with WIN 55212-2. Adolescent exposure to this cannabinoid agonist increased the rewarding effects of 1 mg/kg of cocaine in both HNS and LNS mice, and in HNS mice it also increased the reinstating effect of a low dose of cocaine. Our results endorse a role for individual differences such as a higher propensity for sensation-seeking in the development of addiction.

Corrigendum to "Effects of Cannabinoid Exposure during Adolescence on the Conditioned Rewarding Effects of WIN 55212-2 and Cocaine in Mice: Influence of the Novelty-Seeking Trait".

[This corrects the article DOI: 10.1155/2016/6481862.].

Increased micronuclei and nuclear abnormalities in buccal mucosa and oxidative damage in saliva from patients with chronic and aggressive periodontal diseases.

BACKGROUND AND OBJECTIVE: Periodontal disease is a chronic bacterial infection characterized by connective tissue breakdown and alveolar bone destruction because of inflammatory and immune response caused by periodontopathogens and long-term release of reactive oxygen species. A high number of reactive oxygen species result in periodontal tissue damage through multiple mechanisms such as lipid peroxidation, protein denaturation and DNA damage. The aim of this study was to evaluate DNA and oxidative damage in subjects with chronic or aggressive periodontitis and healthy controls. MATERIAL AND METHODS: Buccal mucosa cells and whole saliva were collected from 160 subjects, who were divided into three groups: subjects with chronic periodontitis (CP) (n = 58), subjects with aggressive periodontitis (AgP) (n = 42) and a control group (n = 60). DNA damage was determined by counting micronuclei (MN) and nuclear abnormalities (NAs) in exfoliated cells, including binucleated cells, cells with nuclear buds and karyolitic, karyorrhectic, condensed chromatin and pyknotic cells. The degree of oxidative stress was determined by quantifying 8-hydroxy-2'-deoxyguanosine (8-OHdG) in whole saliva. RESULTS: Subjects with CP or AgP presented significantly more ( p < 0.05) MN and NAs and higher levels of 8-OHdG ( p < 0.05) compared with the control group. CONCLUSION: Our results indicate that subjects with periodontitis (CP or AgP) exhibited an increase in the frequency of MN, NAs and 8-OHdG, which is directly related to DNA damage. In addition, a positive correlation exists between oxidative stress produced by periodontitis disease and MN.

Substituent and solvent effects on the UV-vis absorption spectrum of the photoactive yellow protein chromophore.

Solvent effects on the UV-vis absorption spectra and molecular properties of four models of the photoactive yellow protein (PYP) chromophore have been studied with ASEP/MD, a sequential quantum mechanics/molecular mechanics method. The anionic trans-p-coumaric acid (pCA(-)), thioacid (pCTA(-)), methyl ester (pCMe(-)), and methyl thioester (pCTMe(-)) derivatives have been studied in gas phase and in water solution. We analyze the modifications introduced by the substitution of sulfur by oxygen atoms and hydrogen by methyl in the coumaryl tail. We have found some differences in the absorption spectra of oxy and thio derivatives that could shed light on the different photoisomerization paths followed by these compounds. In solution, the spectrum substantially changes with respect to that obtained in the gas phase. The n → π1* state is destabilized by a polar solvent like water, and it becomes the third excited state in solution displaying an important blue shift. Now, the π → π1* and π → π2* states mix, and we find contributions from both transitions in S1 and S2. The presence of the sulfur atom modulates the solvent effect and the first two excited states become practically degenerate for pCA(-) and pCMe(-) but moderately well-separated for pCTA(-) and pCTMe(-).

Brief Maternal Separation Inoculates Against the Effects of Social Stress on Depression-Like Behavior and Cocaine Reward in Mice.

Exposure to intermittent repeated social defeat (IRSD) increases the vulnerability of mice to the rewarding effects of cocaine in the conditioned place preference (CPP) paradigm. According to the "inoculation of stress" hypothesis, a brief period of maternal separation (MS) can provide protection against the negative effects of IRSD. The aim of the present study was to assess whether exposure to a brief episode of MS prevents the subsequent short-term effects of IRSD on depression- and anxiety-like behaviors and to explore its long-term effects on cocaine CPP in mice. Four groups of male C57BL/6 mice were employed; two groups were separated from their mother [6 h on postnatal day (PND) 9], while the other two groups were not (controls). On PND 47, 50, 53 and 56, mice that had experienced MS were exposed to social defeat in the cage of an aggressive resident mouse (MS + IRSD group) or were allowed to explore an empty cage (MS + EXPL group). The same procedure was performed with control mice that had not experienced MS (CONTROL + IRSD and CONTROL + EXPL groups). On PND57-58, all the mice performed the elevated plus maze and the hole-board, social interaction and splash tests. Three weeks after the last episode of defeat, all the mice underwent the CPP procedure with cocaine (1 mg/kg). Irrespective of whether or not MS had taken place, a reduction in open arms measures, dips, and social interaction was observed in mice that experienced IRSD. A higher latency of grooming and acquisition of cocaine-induced CPP were observed only in mice exposed to IRSD alone (CONTROL + IRSD). These results suggest that exposure to a brief episode of stress early in life increases the subsequent resilience of animals to the effects of social stress on vulnerability to cocaine.

Intermittent voluntary wheel running promotes resilience to the negative consequences of repeated social defeat in mice.

A novel approach to reduce the incidence of substance use disorders is to promote resilience to stress using environmental resources such as physical exercise. In the present study we test the hypothesis that Voluntary Wheel Running (VWR) during adolescence blocks the negative consequences of stress induced by intermittent repeated social defeat (IRSD). Four groups of adolescent male C57BL/6 mice were employed in the experiment; two groups were exposed to VWR (1 h, 3 days/week) from postnatal day (PND) 21 until the first social defeat (PND 47), while the remaining two groups did not have access to activity wheels (controls). On PND 47, 50, 53 and 56 mice, who had performed VWR, were exposed to an episode of social defeat by a resident aggressive mouse (VWR+IRSD group) or allowed to explore an empty cage (VWR+EXPL group). The same procedure was performed with control mice that had not undergone VWR (CONTROL+IRSD and CONTROL+EXPL groups). On PND 57, all the mice performed the Elevated Plus Maze (EPM), Hole-Board, Social Interaction, Tail Suspension and Splash tests. After an interval of 3 weeks, all mice underwent a conditioned place preference (CPP) procedure with 1 mg/kg of cocaine. Exposure to VWR prevented the negative consequences of social stress in the EPM, splash test and CPP, since the VWR+IRSD group did not display anxiety- or depression-like effects or the potentiation of cocaine reward observed in the Control+IRSD group. Our results support the idea that physical exercise promotes resilience to stress and represents an excellent target in drug abuse prevention.

Role of acute social stress in the rewarding effects of MDMA in adolescent mice.

Drug use among adolescents is a serious problem in our society, as some individuals develop dependence and addiction. MDMA/Esctasy is one of the most typically used substances by this age group. It is well known that environmental factors can alter the rewarding properties of drugs and the propensity to drug-related disorders. In this sense, exposure to social stress induces long-term effects in mice, enhancing the rewarding effects of MDMA in the conditioned place preference (CPP) paradigm. On the other hand, previous research has not provided conclusive results regarding the short-term effects of social defeat on MDMA reward in adolescent animals, probably due to the use of very low or very high doses. Thus, in the present study, we set out to evaluate whether exposure to social defeat immediately before each conditioning session with an intermediate dose of MDMA (2.25 mg/kg) modulates the rewarding effect of this drug in adolescent animals. Our results indicate that both control and socially defeated mice acquired CPP, but only stressed mice showed reinstatement. These findings indicate that social defeat induces an increase in the rewarding effect of MDMA, suggesting that this type of stress is a potential factor in the development of MDMA addiction.

Sleep characterization of a one-month-old freely moving stumptail macaque (Macaca arctoides): a pilot study.

Electroencephalographic (EEG) activity during both human and adult primates' sleep has been proven to be similar and consequently, it could be assessed under similar parameters. However, there is no information regarding this EEG activity in the early stages of development in non-human primates. Therefore, the aim of this study was to describe EEG sleep patterns in a 1-month-old Macaca arctoides with a non-invasive and free-movement method. Sleep stages were initially scored using the criteria of quiet sleep and active sleep. This procedure allowed us to observe graphoelements to distinguish sleep phases as described in adult macaques. Afterwards, the final score was recorded following the Slow Wave Sleep and Rapid Eye Movement Sleep criteria. The present results suggest that sleep features of this monkey are similar to those of a 2-month-old human neonate.

Acute behavioural and neurotoxic effects of MDMA plus cocaine in adolescent mice.

The poly-drug pattern is the most common among those observed in MDMA users, with cocaine being a frequently associated drug. This study evaluates the acute effects of MDMA (5, 10 and 20 mg/kg), alone or in combination with cocaine (25 mg/kg), on motor activity, anxiety (elevated plus maze and social interaction test), memory and brain monoamines in adolescent mice. Both drugs, administered alone or concurrently, produced hyperactivity and a decrease in social contacts. However, an anxiolytic effect, studied by means of the elevated plus maze and expressed as an increase in the time spent on the open arms, was observed only in those animals treated with cocaine and MDMA. The passive avoidance task was affected only with the highest MDMA dose (20 mg/kg). Mice treated with MDMA did not present significant changes in brain monoamines, while those receiving MDMA and cocaine showed a decrease in DA in the striatum, which was accompanied by an increase in the serotonin concentration in the striatum and cortex 30 min after acute administration. In conclusion, the combined use of MDMA and cocaine produces a predominance of serotonin over DA, which is associated with an anxiolytic profile, defensive behaviours and fewer social contacts.

Role of N-methyl-D-aspartate receptors in the long-term effects of repeated social defeat stress on the rewarding and psychomotor properties of cocaine in mice.

Exposure to social stress increases the vulnerability of experimental animals to the rewarding effects of cocaine and it has been suggested that the glutamatergic system could be involved in these effects of stress. The aim of this work is to determine the role of N-methyl-d-aspartate (NMDA) glutamate receptors in the influence of social stress on the conditioned place preference and locomotor sensitization induced by cocaine. Mice treated with saline or NMDA antagonist memantine (5 or 10 mg/kg) underwent repeated social defeat or were kept in the exploration control condition. After three weeks, all groups (SAL + RSD, M5 + RSD, M10 + RSD, SAL + EXP, M5 + EXP and M10 + EXP) were conditioned with 1 mg/kg of cocaine (experiment 1). After nine weeks, each group was subdivided into two groups: one received saline and the other cocaine (25 mg/kg) on 3 consecutive days. After a 5-day interval, all the animals received a challenge of cocaine (10 mg/kg) and their locomotor activity was registered (experiment 2). Only stressed animals developed place preference, an effect prevented by the low dose of memantine. Control defeated mice (but not those treated with memantine) showed greater activity than mice not exposed to stress. Our results show that glutamate NMDA receptors are involved in the higher vulnerability to cocaine effects provoked by exposure to social defeat. They also suggest that memantine could be a useful therapeutic tool for treatment of cocaine dependent individuals exposed to stress conditions.

Behavioural and neurotoxic long-lasting effects of MDMA plus cocaine in adolescent mice.

The poly-drug pattern is the most common among MDMA users, with cocaine being a frequently associated drug. The aim of the present work was to evaluate the behavioural and neurotoxic long-term effects of exposure during adolescence to MDMA alone or plus cocaine. Mice of 28 to 30 days of age received a treatment of two daily injections of an identical dose of MDMA (5, 10 or 20 mg/kg), alone or plus cocaine (25 mg/kg), for 3 days (6 administrations). Three weeks after receiving MDMA, an increase in the time dedicated by the animals to social contacts with their conspecifics was observed, whilst their behaviour in the elevated plus maze showed no differences from that of non-treated mice. After being exposed to MDMA plus cocaine, mice spent more time in social contacts during the interaction test, as well as exhibiting an anxiolytic profile in the elevated plus maze, with an increase in the time and number of entries in the open arms. The activity of mice treated with cocaine alone or plus MDMA remained constant; the decrease observed among the rest of the animals after the second hour was absent in their case. The level of dopamine in the striatum was diminished in mice treated with 20 mg/kg of MDMA, but this neurotransmitter was not affected in animals exposed to the same dose plus cocaine. The present results highlight pronounced alterations in the behaviour of adult mice after exposure to MDMA and cocaine during adolescence, and demonstrate that these long-term effects can occur without the dopaminergic system becoming affected.

Effect of adolescent exposure to MDMA and cocaine on acquisition and reinstatement of morphine-induce CPP.

It is well known that an elevated percentage of ecstasy users also consume cocaine. Recently, it has been reported that a high frequency of heroin smokers first consumed heroin under the effects of ecstasy with the hope of reducing the stimulant effects of the latter drug. The aim of the present study was to evaluate the effect of exposure to MDMA and cocaine during adolescence on morphine-induced conditioned place preference (CPP) and reinstatement in adulthood. In the first experiment, adolescent mice were exposed to six injections of MDMA and three weeks later their response to the reinforcing properties of 40 mg/kg of morphine was evaluated using the CPP paradigm. All the treatment groups developed the same magnitude of morphine-induced preference and, after CPP was extinguished, it was restored in all the groups with a priming dose of 10 mg/kg of morphine. Only mice that had been treated with 10 or 20 mg/kg of MDMA had their morphine-induced preference reinstated after receiving only 5 mg/kg of morphine. In the second experiment, adolescent mice were similarly treated with six administrations of cocaine (25 mg/kg) or cocaine plus MDMA (5, 10 or 20 mg/kg), and their response to morphine-induce CPP was evaluated three weeks later. Similarly to the first experiment, all the groups developed a preference for the morphine-paired compartment, but this preference was not reinstated with a priming dose of 10 mg/kg of morphine following extinction, as was the case among the control animals. These results lead us to hypothesize that periadolescent MDMA exposure alters responsiveness to the rewarding properties of morphine, highlighting MDMA as a gateway drug whose use may increase the likelihood of dependence on other drugs.

Comparative study of six different sludges by sequential speciation of heavy metals.

The presence of heavy metals in the sludges produced in wastewater treatment plants restricts their use for agricultural purposes. This study looks at different types of sludge (aerobic, anaerobic, unstabilised, sludge from a waste stabilisation pond, sludge from an extended aeration plant and heat treated sludge) and compares the distribution of heavy metals with the treatment that they have undergone. In addition, the total quantity of metals (Cd, Cr, Cu, Ca, K, Fe, Mg, Ni, Na, Pb and Zn) and some agronomic parameters necessary for characterising a sludge as suitable for use as amendment were determined. The BCR method for heavy metal speciation was followed. Principal component analysis (PCA) was applied in order to obtain more information about metal speciation in the sewage sludges. It was confirmed that the concentration of heavy metals did not exceed the limits set out by European legislation and that the stabilisation treatment undergone by the sludges strongly influenced the heavy metal distribution and the phases to which they were associated. The waste stabilisation pond sludge, which has undergone a higher degree of mineralisation than the others, shows a lower metal bioavailability index since practically all the heavy metals in it are associated to the oxidisable and residual fraction. On the other hand the unstabilised sludge, which, along with that exposed to extended aeration, contains the highest accumulations of heavy metals in the most easily assimilable fractions.

Characterization and experimental infection of Flexibacter maritimus (Wakabayashi et al. 1986) in hatcheries of post-larvae of Litopenaeus vannamei Boone, 1931.

A preliminary study to characterize filamentous bacteria, whose presence is related to high mortality of Litopenaeus vannamei larvae cultured in Santa Catarina State, Brazil, is reported. The extract of infected larvae was diluted in different concentrations, cultured in marine agar (Difco, Marine Agar 2216) and incubated at 30 degrees C for 48 hours. The biochemical characterization included hydrolytic reactions of starch, gelatin and tyrosine, growth in TCBS agar, growth in 0 and 37 per thousand salinity, pigment production in tyrosine agar, production of H2S, nitrate reduction, congo red reaction, oxidase and catalase. The isolated bacteria belong to the species Flexibacter maritimus, Gram-negative bacilli of 0.4-0.5 microm width and 15 microm length. Experiments were carried out on pathogenicity of F. maritimus in post-larvae of L. vannamei. Survival and symptoms in L. vannamei post-larvae 24 hours after inoculation with F. maritimus and its growth in marine agar were evaluated. Mortality was detected around 92,5% as well as symptoms like melanized lesions in several parts of body, discolouration of gills, bad formation of appendages and of the last abdominal segment, low motility and feeding reduction. The experimental infection results suggested that isolated bacteria of the genus Flexibacter are pathogenic to the shrimp Litopenaeus vannamei post-larvae.

Role of AMPA glutamate receptors in the conditioned rewarding effects of MDMA in mice.

Currently, there is not an effective treatment for 3,4-methylenedioxymethamphetamine (MDMA) dependence but pharmacotherapies targeting glutamate neurotransmission are a promising strategy. Previously, we showed that blockade of glutamate NMDA and AMPA receptors impairs the conditioned rewarding effects of MDMA and cocaine, respectively. In this study we evaluated the role of AMPA receptors in the rewarding effects of MDMA in mice using the conditioned place preference (CPP) paradigm. Mice were conditioned with MDMA (1.25 mg/kg) 60 min after the treatment with saline or different doses (0.25, 1 and 5 mg/kg) of the AMPA/kainate receptor antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Mice conditioned with MDMA acquired CPP while those treated with any dose of CNQX + MDMA did not. These results supported the involvement of the glutamatergic system in the rewarding properties of MDMA, and suggest that AMPA receptor blockade could be a new therapeutic option for the treatment of those individuals that develop MDMA dependence.

Effect of memantine and CNQX in the acquisition, expression and reinstatement of cocaine-induced conditioned place preference.

The present study evaluates the effect of memantine, a non-competitive N-methyl-d-aspartate (NMDA) glutamate receptor antagonist and CNQX, an alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA)/kainate receptor antagonist on the rewarding effects of cocaine in mice, using the conditioned place preference (CPP) paradigm. Cocaine-induced CPP was studied pairing this drug with different memantine or CNQX doses during either the acquisition or the expression phase of the procedure. Once CPP was established, and the preference extinguished, reinstatement was induced by a priming dose of cocaine. Both antagonists, which in themselves do not present motivational actions on the preference shown by the animals, abolished the acquisition and expression of the cocaine-induced CPP. Neither of the antagonists precipitated reinstatement of the preference induced by cocaine but memantine blocked the cocaine-primed reinstatement. Our results suggest that cocaine-induced CPP and reinstatement is largely dependent on glutamate neurotransmission, and confer a putative role for memantine among the tools useful for cocaine management and treatment.

[The influence of social stress on the reinforcing effect of ecstasy under the conditioned place preference paradigm: the role played by age, dose and type of stress]. / Influencia del estres social en el efecto reforzante del extasis bajo el paradigma de condicionamiento de preferencia de lugar: papel de la edad, la dosis y el tipo de estres.

INTRODUCTION: Addiction to drugs is a chronic illness with severe repercussions for those that consume them and to date has no known cure. Psychostimulants, such as ecstasy, are the most widely consumed illegal drugs among adolescents and young adults. AIMS: To describe and to analyse the different variables that can influence the effects of social stress and the reinforcing properties of ecstasy. Likewise, it also seeks to evaluate whether the effects of social stress on conditioned place preference (induced by ecstasy) are similar to those deriving from other psychostimulants, such as cocaine. DEVELOPMENT: Social defeat evaluated in the short term has an effect only on adult animals by diminishing sensitivity to the conditioned reinforcing effects of ecstasy. Conversely, long-term social stress increases the reinforcing effects of this drug in adolescent and adult animals. The dose of ecstasy employed has little influence on the effects of social defeat on conditioned place preference. In comparison to the effects of social stress on the reinforcing properties of cocaine, a different effect is only observed when defeat is evaluated in the short term. CONCLUSIONS: Different variables modulate the reinforcing effects of ecstasy, such as the age of the animals, the dose employed or exposure to stress. It is essential to study these variables in order to determine the neurobiological and environmental vulnerability factors that can have an influence on the development of addiction to ecstasy.

TITLE: Influencia del estres social en el efecto reforzante del extasis bajo el paradigma de condicionamiento de preferencia de lugar: papel de la edad, la dosis y el tipo de estres.Introduccion. La adiccion a las drogas es una enfermedad cronica con graves repercusiones para sus consumidores y que hasta el momento no tiene curacion. Los psicoestimulantes, como el extasis, son las drogas ilegales mas consumidas, tanto por los adolescentes como por los adultos jovenes. Objetivos. Describir y analizar diferentes variables que pueden influir en los efectos del estres social y las propiedades reforzantes del extasis. Asimismo, se pretende evaluar si los efectos del estres social sobre el condicionamiento de preferencia de lugar (inducido por el extasis) son similares a los que ejercen otros psicoestimulantes, como la cocaina. Desarrollo. La derrota social evaluada a corto plazo solo ejerce un efecto en animales adultos, disminuyendo la sensibilidad a los efectos reforzantes condicionados del extasis. Por el contrario, el estres social a largo plazo incrementa los efectos reforzantes de esta droga en animales adolescentes y adultos. La dosis de extasis utilizada ejerce una escasa influencia en los efectos de la derrota social sobre el condicionamiento de preferencia de lugar. En comparacion con los efectos del estres social sobre las propiedades reforzantes de la cocaina, unicamente se observa un efecto diferente cuando la derrota es evaluada a corto plazo. Conclusiones. Existen diferentes variables que modulan los efectos reforzantes del extasis, como la edad de los animales, la dosis utilizada o la exposicion al estres. El estudio de todas estas variables es esencial para determinar los factores de vulnerabilidad neurobiologicos y ambientales que pueden influir en el desarrollo de dependencia al extasis.

Role of nitric oxide pathway in the conditioned rewarding effects of MDMA in mice.

It is estimated that 2.1 million young adults used MDMA/Ecstasy in the last year in Europe. Vulnerable subjects can develop dependence after MDMA abuse but currently there does not exist an effective treatment for this disorder. The nitric oxide (NO) pathway seems to have an important role on the rewarding effects of different drugs and has been proposed as a new pharmacological treatment for psychostimulant addiction. In the present study, we intend to evaluate whether the blockade of the NO synthesis (NOS) interferes with the rewarding effects of MDMA in the conditioned preference place (CPP) paradigm in young adult male mice. Our results indicated that mice treated with 7-nitroindazole (a NOS inhibitor) did not show CPP after conditioning with MDMA (1.25mg/kg). These results demonstrated the role of the NO pathway in the rewarding effects of MDMA and suggested that the manipulation of this pathway could be a new therapeutic option for MDMA abuse.