The Influence of Placebo Effect on Craving and Cognitive Performance in Alcohol, Caffeine, or Nicotine Consumers: A Systematic Review.

OBJECTIVE: The present systematic review aims to analyze the evidence about the influence of placebo effect on craving and cognitive performance in alcohol, caffeine, and nicotine consumers. METHODS: Relevant studies were identified via Pubmed, Web of Science, and Scopus databases (up to March 2020). Only those papers published between 2009 and 2019 were searched. RESULTS: Of the 115 preliminary papers, 8 studies of database search and 9 of the manual search were finally included in this review. Findings showed that while alcohol expectancies increased craving, caffeine and nicotine expectancies tend to decrease it. Alcohol expectancies caused similar or slower reaction time when alcohol was not consumed, impairments on inhibitory control (especially after alcohol consumption) and similar post-error slowing. The effect of caffeine and nicotine on reaction time has not been elucidated yet, however, caffeine expectancies have been shown to improve accuracy and the attentional filtering of distracting stimuli. CONCLUSIONS: Alcohol, caffeine, and nicotine expectancies play an important role on craving. Although expectancies produce an effect on cognitive performance, caffeine and nicotine beliefs show an ambiguous impact on reaction time. Only the influence of alcohol expectancies on reaction time has been clarified. Furthermore, caffeine beliefs enhance accuracy.

Respuesta placebo en la enfermedad de Parkinson: una revisión teórica / Placebo response in Parkinson's disease: A theoretical review

La enfermedad de Parkinson es un trastorno neurodegenerativo que se caracteriza por la presencia de temblor en reposo, bradicinesia y rigidez como consecuencia de la pérdida de neuronas dopaminérgicas en la vía nigroestriatal. El objetivo de esta revisión teórica es examinar la respuesta placebo en la enfermedad de Parkinson, recopilando los estudios publicados desde el año 2000 hasta la actualidad mediante una búsqueda bibliográfica en las bases de datos Medline, Psycinfo y Scopus. Los resultados indican que, aunque suele haber una clara respuesta a la medicación antiparkinsoniana, con mejora de los síntomas motores de la enfermedad, también se han observado mejoras significativas a nivel motor tras la administración de placebo, si bien generalmente estos cambios son de corta duración. Se señalan también algunas limitaciones potenciales de esta revisión y la importancia que la respuesta placebo tiene tanto para el diseño de trabajos de investigación como desde el punto de vista clínico

Parkinson's disease is a neurodegenerative disorder characterized by the presence of tremor at rest, bradykinesia and rigidity as a consequence of the selective loss of dopaminergic neurons of the nigrostriatal pathway. The objective of this theoretical review is to examine the placebo response in Parkinson's disease, compiling the information referring to the studies published from year 2000 until the present time by an electronic search in Medline, Psycinfo and Scopus databases. Results indicate that, although there is usually a clear response to antiparkinsonian medication, showing an improvement of the motor symptoms of the disease, significant improvements have also been observed at the motor level in response to the administration of placebo, although generally these changes are of short duration. Finally, some potential limitations of this review are pointed out, and the importance that the placebo response has both for experimental designs and from the clinical point of view

Effects of para-methoxyamphetamine (PMA) on agonistic encounters between male mice.

Para-methoxyamphetamine (PMA) is a synthetic drug chemically similar to the recreational drug 3,4-methylenedioxy-methamphetamine (MDMA or "ecstasy") and often replaces MDMA in tablets that show an "ecstasy" logo. PMA displays a higher toxic potential than MDMA, but the behavioral profile of PMA has been scarcely studied in animal models. Here we evaluated the effects of PMA (2, 4, 8, and 12 mg/kg, i.p.) on agonist encounters between male mice using an ethopharmacological approach, the isolation-induced aggression model. Likewise, since PMA and MDMA share common mechanisms of action, we compared the behavioral profile of PMA with that induced by MDMA (8 mg/kg, i.p.) which behavioral effects in this model are well characterized. Individually housed mice were exposed to anosmic standard opponents 30 min after drug administration. The encounters were videotaped and evaluated using an ethologically based analysis. PMA (all doses) significantly reduced offensive behaviors (threat and attack), however, a detailed behavioral analysis suggests that the observed antiaggressive effect seems to be unspecific, showing a complex dose-dependent behavioral profile. Thus, antiaggresive actions observed after the administration of the lowest dose were accompanied by increases in social investigation, avoidance/flee behaviors and non-social explorations, together with a reduction of digging behavior. This pattern reflects both approach-contact behaviors and avoidance-flee behaviors. From 4 mg/kg to 12 mg/kg, the increase in social investigation previously observed disappears, and there is a slight increase in immobility, together with a different behavioral pattern that suggests anxiogenic effects of PMA, similar to those reported after the administration of MDMA. The higher doses of PMA exhibit a behavioral profile very similar to that observed in animals treated with MDMA, with the exception of the immobility produced by PMA. These findings show for the first time the non-specific antiaggressive profile of PMA in the model of aggression induced by isolation in male mice.

Selective agonism of mGlu8 receptors by (S)-3,4-dicarboxyphenylglycine does not affect sleep stages in the rat.

BACKGROUND: Metabotropic glutamate receptors (mGlu) play a role in a number of physiological processes and behaviors, as well as in certain pathological conditions and diseases. New drugs targetting mGlu receptors are being developed with treatment purposes. Recent data indicates that glutamate is involved in sleep, and pharmacological manipulation of distinct subtypes of mGlu receptors affect sleep. Here the consequences of selective pharmacological agonism of mGlu8 receptor upon sleep and wakefulness are explored for the first time. METHODS: 32 male Wistar rats were stereotaxically prepared for polysomnography. (S)-3,4-dicarboxyphenylglycine (S)-3,4-DCPG (5, 10, and 20mg/kg, ip), a selective and potent mGlu8 receptor agonist, or physiological saline was administered one hour after the light period began. RESULTS: Compared to control vehicle, (S)-3,4-DCPG, did not affect, at any of the doses given, the sleep and wakefulness parameters examined in the general analysis of the three hours of recording. Drug effects across time were studied analyzing three one-hour time blocks, control and experimental groups did not show any significant difference in the sleep and wakefulness parameters analyzed. Latency to sleep stages did not significantly vary between vehicle and treatment groups. CONCLUSIONS: Results indicate that pharmacological activation of mGlu8 receptor by (S)-3,4-DCPG (5, 10, 20mg/kg, ip) does not affect sleep and wakefulness in the rat, suggesting that pharmacological agonism of these receptors may not influence sleep. Further research is needed to verify whether new drugs acting on these receptors lack of effect upon sleep and wakefulness.

Estudio de la instigación social en un modelo de agresión inducida por aislamiento: efectos de la administración de JNJ16259685, un antagonista de receptores mGlu1 / Study of the Social Instigation in a Model of Isolation-Induced Aggression: Effects of JNJ16259685 Administration, an mGlu1 Receptor Antagonist

La instigación social intensifica la conducta agresiva permitiendo observar niveles más extremos de agresión. Estudios recientes indican que el receptor metabotrópico del glutamato mGlu1 está implicado en la regulación de la conducta agresiva en un modelo de agresión inducida por aislamiento. El objetivo de este trabajo fue evaluar los efectos de la administración de un antagonista del receptor mGlu1 (JNJ16259685) sobre la conducta agresiva normal e intensificada, utilizando instigación social en un modelo animal de agresión inducida por aislamiento. Varios grupos de animales aislados fueron expuestos a 5 minutos de instigación social, recibiendo la mitad de ellos JNJ16259685 (0.5 mg/kg, ip) o vehículo. Las interacciones agonísticas de 10 min de duración se realizaron en un área neutral 30 min después de la inyección. Dichos encuentros fueron grabados en vídeo para el posterior análisis etológico de diez categorías conductuales. La instigación redujo la latencia de ataque y aumentó la frecuencia y duración de los ataques frente a los animales no instigados. La administración de JNJ16259685 redujo de forma significativa la conducta agresiva en ambos casos, sugiriendo la implicación del receptor mGlu1 en la modulación de la agresión normal e intensificada.

Social instigation intensifies aggressive behavior in rodents allowing observe more extreme levels of aggression. Recent studies indicate that glutamate metabotropic receptor 1 (mGlu1) are involved in the regulation of aggressive behavior in isolation-induced aggression model. The object of this work was to examine social instigation in an animal model of isolation-induced aggression and assess the anti-aggressive effects of an mGlu1 receptor antagonist (JNJ16259685) on normal and heightened aggressive behavior. Several groups of individually housed mice were exposed to 5 minutes of social instigation, and half of them received an acute administration ofJNJ16259685 (0.5 mg/kg, ip) or vehicle. Ten minute of dyadic interactions were staged between a singly housed and an anosmic mouse in a neutral area 30 min after drug or vehicle administration. The encounters were videotaped for subsequent analysis of ten ethological behavioural categories. Social instigation reduced latency of attack and increased the frequency and duration of attacks against not instigated animals. JNJ16259685 administration significantly reduced aggressive behavior in both cases, suggesting the involvement of mGlu1 receptor in the modulation of normal and heightened aggression.

Effects of MPEP, a selective metabotropic glutamate mGlu5 ligand, on sleep and wakefulness in the rat.

Metabotropic glutamate receptors (mGlu) have been implicated in the regulation of physiological and behavioral processes. Pharmacological evidence involves group I mGlu receptors in the regulation of emotional states and antagonism of these receptors has been proposed as a novel class of anxiolytic drugs having also antidepressant effects. Here, the effects of mGlu5 receptor selective modulation on sleep and wake states are explored. 32 male Wistar rats were implanted with electrodes for recording sleep and wake states. 2-Methyl-6-(phenylethynyl)pyridine hydrochloride (MPEP hydrochloride, 5, 10, and 20 mg/kg, i.p.), a potent, selective and systemically active mGlu5 receptor negative allosteric modulator, or vehicle was administered 1 h after the beginning of the light period. Sleep recordings were conducted for 3 h. MPEP (5, 10, and 20 mg/kg) significantly suppressed rapid eye movement (REM) sleep, decreasing the number of episodes and mean episode duration, and increased its latency. A reduction of light and deep slow wave sleep (SWS) latency was observed in the groups receiving 10 or 20 mg/kg, increasing latency to first wakefulness episode. 10 mg/kg of MPEP also increased non rapid eye movement sleep (NREM). The present results suggest that mGlu5 receptors might be involved in sleep regulation, more specifically in REM sleep, and drugs that block these receptors could potentially benefit the treatment of pathologies were REM sleep is enhanced.

Positive allosteric modulation of mGlu7 receptors by AMN082 affects sleep and wakefulness in the rat.

Evidence indicates that metabotropic glutamate receptors (mGlu) are involved in the regulation of physiological and behavioral processes, and glutamate has been implicated in several pathologies of the Central Nervous System. Pharmacological evidence suggests the therapeutic potential of targeting mGlu7 receptor in a number of pathological conditions; and previous research has shown the involvement of glutamate on sleep and wakefulness regulation. Here, the effects of mGlu7 receptor selective modulation on sleep and wake states are explored. 32 male Wistar rats were implanted with electrodes for recording sleep and wakefulness. N,N'-Bis(diphenylmethyl)-1,2-ethanediamine dihydrochloride (AMN082) (5, 10, and 20mg/kg, i.p.), a potent, selective and systemically active mGlu7 receptor positive allosteric modulator, or vehicle was administered 1 hour after the beginning of the light period. AMN082 (5 and 10mg/kg) significantly increased total time of sleep; and time spent on Slow Wave Sleep (SWS) was increased. AMN082 at 10mg/kg specifically affected Light SWS, increasing time spent on Light SWS. The highest dose of AMN082, 20mg/kg, significantly reduced time spent in Rapid Eye Movement (REM) sleep, decreasing the number of REM sleep episodes and their mean duration. Total time spent awake was increased and mean episode duration of wakefulness was prolonged. The present results suggest that mGlu7 receptors might be involved in sleep regulation and drugs targeting these receptors could affect sleep and wakefulness architecture.

Effects of (+) SKF 10,047, a sigma-1 receptor agonist, on anxiety, tested in two laboratory models in mice / Efectos Efectos del (+)SKF 10,047, un agonista del receptor sigma-1, sobre la ansiedad evaluada en dos modelos de laboratorio en ratones

Recently, sigma-1 receptor modulators have been considered drugs with an interesting therapeutic potential for the treatment of anxiety. However, there is no clear information in preclinical studies about the possible effects of sigma-1 ligands on anxiety in experimental animal models. Therefore, the present study examined the effects of (+)SKF 10,047 (2-8 mg/kg, ip), a sigma-1 agonist, on anxiety, tested in two classical laboratory models (social interaction test and elevated plus maze). (+)SKF 10,047 (8 mg/kg) produced a significant decrease of social investigation in the «social interaction test», whereas in the «elevated plus maze», the drug (4 and 8 mg/kg) provoked a significant reduction in the number of entries into open arms, as well as in the time spent in this area, as compared with the control group, without affecting motor activity. Overall, these findings indicate that (+)SKF 10,047 exhibits an anxiogenic-like profile in mice. It is suggested that anxiogenic effects of this sigma-1 ligand could be related to its potent ability to modulate diverse neurotransmitter systems involved in anxiety regulation (AU)

Los receptores sigma-1 han sido considerados recientemente como fármacos con un interesante potencial terapéutico para el tratamiento de la ansiedad. Sin embargo, no existe información clara en estudios preclínicos con respecto a los posibles efectos de los ligandos sigma-1 sobre la ansiedad en modelos animales experimentales. Por lo tanto, en este trabajo examinamos los efectos de la administración de (+)SKF 10,047 (2-8 mg/kg, ip), un agonista sigma-1, sobre la ansiedad evaluada en dos modelos clásicos de laboratorio (test de interacción social y laberinto elevado en cruz). (+)SKF 10,047 (8 mg/kg) produjo una reducción significativa de las conductas de investigación social en el «test de interacción social», mientras que en el laberinto elevado en cruz el fármaco provocó (4 y 8 mg/kg) una disminución significativa del número de entradas y del tiempo pasado en los brazos abiertos del laberinto, en comparación con el grupo control, sin afectar la actividad motora. Estos resultados indican que el (+)SKF 10,047 muestra un perfil ansiogénico en ratones. Se sugiere que los efectos ansiogénicos de este ligando sigma-1 podrían estar relacionados con su potente capacidad para modular diferentes sistemas de neurotransmisión implicados en la regulación de la ansiedad (AU)

Effects of (+) SKF 10,047, a sigma-1 receptor agonist, on anxiety,tested in two laboratory models in mice.

Recently, sigma-1 receptor modulators have been considered drugs with an interesting therapeutic potential for the treatment of anxiety. However, there is no clear information in preclinical studies about the possible effects of sigma-1 ligands on anxiety in experimental animal models. Therefore, the present study examined the effects of (+)SKF 10,047 (2-8 mg/kg, ip), a sigma-1 agonist, on anxiety, tested in two classical laboratory models (social interaction test and elevated plus maze). (+)SKF 10,047 (8 mg/kg) produced a significant decrease of social investigation in the "social interaction test", whereas in the "elevated plus maze", the drug (4 and 8 mg/kg) provoked a significant reduction in the number of entries into open arms, as well as in the time spent in this area, as compared with the control group, without affecting motor activity. Overall, these findings indicate that (+)SKF 10,047 exhibits an anxiogenic-like profile in mice. It is suggested that anxiogenic effects of this sigma-1 ligand could be related to its potent ability to modulate diverse neurotransmitter systems involved in anxiety regulation.

Efectos de la administracion de MPEP, un antagonista selectivo de los receptores de glutamato mGlu5, sobre la memoria espacial en ratones / Effects of administration of MPEP, a selective mglu5 receptor antagonist, on spatial memory in mice

Estudios recientes han mostrado que la inhibición de los receptores mGlu5 perjudica el aprendizaje espacial evaluado con una tarea en el laberinto acuático con ratones, lo que indica una implicación de estos receptores en el aprendizaje y la memoria. En un intento por esclarecer la participación de los receptores mGlu5 en los procesos de aprendizaje, hemos examinado los efectos de 2-metil-6-(feniletinil)piridina (MPEP; 10 mg/kg, intraperitoneal), un antagonista selectivo de los receptores de glutamato mGlu5, en el aprendizaje espacial de ratones macho de la cepa OF.1. Para ello, empleamos una tarea de aprendizaje en el laberinto de hoyos adaptada a ratón, que nos permite valorar simultáneamente la memoria de trabajo (MT) y la memoria de referencia (MR) espacial. El laberinto de hoyos consiste en un campo abierto que consta de 16 hoyos. Durante los ensayos, la misma configuración de 4 hoyos reforzados permanece constante durante el entrenamiento. Los animales deberían aprender a visitar sólo las localizaciones reforzadas y hacerlo una sola vez, recordando la lista de lugares ya visitados para evitar las revisitas. Nuestros resultados mostraron que los ratones adquirieron fácilmente este hábito a los 5 días (4 ensayos por día). El último día, 30 min antes del entrenamiento, los animales fueron tratados con solución salina (grupo control) o con MPEP. No encontramos diferencias significativas entre ambos grupos. Estos hallazgos indican que la administración aguda de MPEP (10 mg/kg) no afecta la MT y la MR espacial en ratones macho. Se hacen necesarios otros estudios con mayores dosis del fármaco y otras situaciones de prueba para confirmar estos resultados

Recent studies have found that mGlu5 receptor blockade impairs spatial learning tested in a water maze task in mice, suggesting that these receptors might play a role in learning and memory. To clarify the involvement of mGlu5 receptors in spatial learning processes, we examined the effects of 2-methyl-6-(phenylethylnyl) pyridine (MPEP; 10 mg/kg, i.p.), a selective mGlu5 receptor antagonist, on spatial learning in male mice of the OF.1 strain. To do this, we adapted a hole-board-learning task to mice. This task allows simultaneous assessment of spatial working memory (WM) and reference memory (RM) performance. The hole-board apparatus consists of an open-field with a 16-hole floor. During the trials, a configuration of 4 holes baited with a food pellet was unchanged throughout training. The animals had to learn to visit only baited locations and to visit them only once, remembering a list of places already visited in order to avoid revisits. Our results showed that the mice readily acquired this task within 5 days (4 trials per day). On the last day, 30 minutes before training, the animals were administered either saline solution (control group) or MPEP. No significant differences were found between the two groups. These findings indicate that acute administration of MPEP (10 mg/kg) did not affect spatial WM or RM in male mice. Further studies with higher doses of the drug and other test situations are required to confirm these results (AU)

Ácidos grasos omega-3 y enfermedades neuropsiquiátricas / Omega-3 fatty acids and neuropsychiatric disorders

Los ácidos grasos poliinsaturados omega-3 desempeñan un destacado papel en el correcto funcionamiento de la membrana neuronal. Numerosos estudios sugieren que el consumo de suplementos de estos compuestos (especialmente ácido eicosapentanoico [EPA] y ácido docosahexanoico [DHA]) podría producir una mejoría clínica en algunas enfermedades neuropsiquiátricas. En este trabajo se presenta una revisión actualizada de la evidencia disponible en relación con el uso de ácidos grasos omega-3 en el tratamiento de la esquizofrenia, la depresión, el trastorno bipolar y otras enfermedades neuropsiquiátricas

Omega-3 polyunsaturated fatty acids play a major role in the correct functioning of the neuronal membrane. Numerous studies suggest that the consumption of omega-3 fatty acid supplements (especially eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) could produce a clinical improvement in some neuropsychiatric disorders. This article presents an updated review of the evidence available on the use of these compounds in the treatment of schizophrenia, depression, bipolar disorder, and other neuropsychiatric abnormalities

Effects of selective dopamine D4 receptor antagonist, L-741,741, on sleep and wakefulness in the rat.

The influence of the dopamine system upon sleep/wake states is not fully understood. To date, the role of dopamine D4 receptor has not been studied. The aim of this work is to study the influence of dopamine D4 receptor upon sleep/wake states in male rats. Male Wistar rats were implanted with electroencephalography and electromyography electrodes for sleep recording. Sleep/wake times were compared in rats first treated with control solution (vehicle) and the day after treated with a potent and highly selective D4 dopamine receptor antagonist. L-741,741 (1.5, 3, 6 mg/kg) or vehicle solution (10% DMSO in saline) was administered intraperitoneally at the beginning of the light period. Subsequently, 3 h of polysomnography were recorded and sleep-wake parameters evaluated. For statistical comparisons, Wilcoxon ranges test was performed. L-741,741 (1.5 mg/kg) only increased Light Slow Wave Sleep (SWS). 3 mg/kg enhanced Quiet Waking (QW) increasing number of episodes, whereas Active Waking (AW) was reduced decreasing mean episode duration. 6 mg/kg reduced number of episodes of Deep SWS and increased its latency. Light SWS was decreased reducing number of episodes and their duration. Total time spent asleep was reduced and time spent in AW was increased. REM latency was increased. These results suggest a role for D4 receptors in the regulation of wake and sleep.

Effects of selective neuronal nitric oxide synthase inhibition on sleep and wakefulness in the rat.

The role played by the unconventional messenger Nitric Oxide (NO) upon the sleep-wake cycle remains controversial. Evidence suggests a positive role of NO on Slow Wave Sleep (SWS) and Paradoxical Sleep (PS) regulation, favoring sleep. However, other studies have found a role of NO upon wakefulness and alertness, inhibiting sleep. Divergences have been explained in part because of the use of different inhibitors of nitric oxide synthases (NOS). The aim of this study is to analyse the effects of a highly selective neuronal NOS inhibitor (3-Bromo7-Nitroindazole) on sleep-wake states in rats. Male Wistar rats were stereotaxically prepared for polysomnography. 3-Bromo-7-Nitroindazole (10, 20, 40 mg/kg, i.p.) dissolved in DMSO 10% filled with saline, or vehicle (DMSO 10% in saline) was administered at the beginning of the light period. Three hours of polygraphic recordings were evaluated for stages of vigilance. Results show dose-dependent effects of 3-Bromo7-Nitroindazole upon sleep: 10 mg/kg decreases duration and number of episodes of deep SWS, increasing duration of light SWS. 20 mg/kg decreased duration of light and deep SWS, while active and quiet wake increased. Deep SWS and PS latency increased. Number of episodes of PS decreased, as well as number of cycles of sleep and time spent asleep. 40 mg/kg reduced duration of deep SWS and increased mean episode duration of light SWS. Therefore, sleep states are affected by selective inhibition of nNOS, reducing in all cases deep SWS. These results support the hypothesis that nitric oxide, produced by nNOS, is involved in sleep processes, favoring sleep.

Behavioural effects of dimethyl sulfoxide (DMSO): changes in sleep architecture in rats.

Dimethyl sulfoxide (DMSO) is an efficient solvent for water-insoluble compounds, widely used in biological studies and as a vehicle for drug therapy, but few data on its neurotoxic or behavioural effects is available. The aim of this work is to explore DMSO's effects upon sleep/wake states. Twenty male rats were sterotaxically prepared for polysomnography. Four concentrations of DMSO (5%, 10%, 15%, and 20%, in saline) were examined. DMSO or saline were administered intraperitoneally at the beginning of the light period. Three hours of polygraphic recording were evaluated for stages of vigilance after treatment. Sleep/wake parameters and EEG power spectral analyses during sleep were investigated. Results show no significant effect after 5% or 10% DMSO treatment. DMSO 15% increased mean episode duration of light slow wave sleep (SWS), decreasing mean episode duration of deep SWS and of quiet wake (QW). DMSO 20% increased light SWS enhancing number of episodes, while decreased deep SWS mean episode duration. EEG power spectra of sigma and delta activity were also affected by DMSO. Therefore, DMSO at 15% and 20% affects sleep architecture in rats, increasing light SWS and reducing deep SWS. Being aware of DMSO behavioural effects seems important since experimental artefacts caused by DMSO can lead to the erroneous interpretation of results.

Anxiogenic-like activity of 3,4-methylenedioxy-methamphetamine ("Ecstasy") in the social interaction test is accompanied by an increase of c-fos expression in mice amygdala.

3,4-Methylenedioxymethamphetamine (MDMA) is a synthetic amphetamine popularly known as "Ecstasy." Animal studies examining acute effects of MDMA on anxiety are unclear because although an anxiolytic-like action of MDMA in different animal models of anxiety has been described, there is also substantial evidence supporting an anxiogenic-like effect of this drug. To date, several studies have examined c-fos expression following MDMA administration in rats. However, there is no information about the MDMA-induced c-fos expression in mice previously tested in an animal model of anxiety. In this study, male mice were injected with MDMA (1, 8 and 15 mg/kg ip) and assessed for changes on anxiety and for the expression of the immediate early gene c-fos in the amygdala (central, basolateral and basomedial). Anxiety was evaluated by the "social interaction test." Ten behavioral categories were recorded: body care, digging, nonsocial exploration, exploration from a distance, social investigation, threat, attack, avoidance/flee, defense/submission and immobility. As compared with the control group, mice treated with MDMA (all doses) showed a decrease in mean duration and total time spent in social investigation behaviors, whereas avoidance/flee behaviors were significantly increased after treatment with this compound (8 and 15 mg/kg). Likewise, a significant increase in c-fos expression was found in the basolateral (all doses) and central (15 mg/kg) amygdala after MDMA administration. Overall, these findings indicate that MDMA exhibits an anxiogenic-like profile in the social interaction test in mice, and that central and basolateral amygdala might be involved in these anxiogenic-like effects of the drug.

Cytochrome oxidase activity of the suprachiasmatic nucleus and pineal gland in rats with portacaval shunt.

Rhythmic behavioral and biochemical changes have been observed in both human and animal models with hepatic insufficiency. The basis of all these alterations is the principal endogenous pacemaker, the suprachiasmatic nucleus. The aim of this work, therefore, is to determine cytochrome c oxidase activity, a marker of neuronal activity and oxidative metabolism, in this nucleus in rats with portacaval shunt. In order to do this, this enzyme was histochemically marked and quantified by computer-assisted optical densitometry. Results show a reduced cytochrome oxidase activity in the suprachiasmatic nucleus in animals with portacaval shunts and, inversely, an increase in oxidative metabolism in the pineal gland, another circadian structure. However, the activity measured in a noncircadian brain structure, the hippocampus, which served as a control, showed no changes with surgery. Additionally, locomotor activity was assessed by actimeters and revealed a clearly reduced activity in animals with portacaval shunt. We conclude that the suprachiasmatic nucleus is possibly involved in the rhythmic changes associated with hepatic insufficiency.

Coadministration of L-NOARG and tiapride: effects on catalepsy in male mice.

This study was designed to determine the possible potentiation of catalepsy behavior after coadministration of N(G)-nitro-L-arginine (L-NOARG), an inhibitor of nitric oxide synthase (NOS), and tiapride, a specific antagonist for D2 receptors, in male mice. Catalepsy was measured by the bar test. Two successive evaluations were carried out 60 and 90 min after injections. The induction of catalepsy following coadministration of L-NOARG (25 and 50 mg/kg) and tiapride (200 mg/kg) was significantly higher than the sum of catalepsy scores after administration of L-NOARG and tiapride separately. Coadministration of L-NOARG and tiapride produced a clear potentiation of their effects on catalepsy in mice. These results underline the view that nitric oxide (NO) interacts with central dopamine D2 transmission.

Tratamiento psicofarmacológico de los trastornos de personalidad / Psychopharmacological treatment of personality disorders

Recientes investigaciones psicobiológicas indicar que la farmacoterapia podría ser de utilidad para el tratarniento de los trastornos de personalidad. En este artículo, presentamos una revisión de los resultados de los estudios psicofarmacológicos publicados de acuerdo a la categorización del eje II del DSM-IV, que clasifica a los trastornos de personalidad en tres grupos: A (paranoide, esquizoide y esquizo-típico), B (antisocial, límite, histriónico y narcisista) y C (dependiente, evitación y obsesivo-compulsivo) Aunque se han realizado pocos estudios controlados en el Grupo A, la evidencia disponible sugiere que la administración de dosis bajas de antipsicóticos podría ser de utilidad en estos pacientes La mayor parte de los tra-bajos se ha llevado a cabo en sujetos del grupo B, y especialmente en el trastorno límite de la personalidad, donde se han comunicado resultados parcialmente positivos utilizando neurolépticos, antidepresivos, benzodiazepinas (alprazolam) y fármacos antimaniacos. Finalmente, en el grupo C, algunos estudios aislados sugieren un efecto clínico favorable tras la administración de antidepresivos (especialmente ISRS y venlafaxina) y benzodiazepinas (AU)