Ultradian cycles in mice: definitions and links with REMS and NREMS.

Sleep can be organized in two quite different ways across homeothermic species: either in one block (monophasic), or in several bouts across the 24 h (polyphasic). Yet, the main relationships between variables, as well as regulating mechanisms, are likely to be similar. Correlations and theories on sleep regulation should thus be examined on both types of sleepers. In previous studies on monophasic humans, we have shown preferential links between the number of ultradian cycles and the rapid eye movement sleep (REMS) time, rather than with its counterpart non-rapid eye movement sleep (NREMS). Here, the sleep of 26 polyphasic mice was examined, both to better describe the NREMS distribution, which is far more complex than in humans, and to replicate the analyses performed on humans. As in humans, the strongest links with the number of cycles were with REMS. Links were not significant with NREMS taken as a whole, although positive correlations were found with the NREMS immediately preceding REMS episodes and inversely significant with the residue. This convergence between monophasic and polyphasic patterns supports the central role played by REMS in sleep alternation.

Early visual components (P100, N170) are disrupted in chronic schizophrenic patients: an event-related potentials study.

INTRODUCTION: On the basis of the Positive and Negative Syndrome Scale (PANSS), fourteen schizophrenic patients and 7 normal controls were confronted with pictures from the Ekman & Friesen series in an event-related potentials study. PROCEDURE: Participants were confronted with a visual face-detection task, in which they had to detect, as quickly as possible, deviant faces amongst a train of standard stimuli (neutral faces). Deviant faces changed either on identity (different identity, neutral expression), or on emotion (same identity, happy, fearful or sad expression). RESULTS: Schizophrenics exhibited a decrease in amplitude of the face N170, recorded around 170 ms at occipito-temporal sites; this was observed as well for emotional as for identity faces, which suggests a global involvement of face processing. Moreover, this decrease of the face-N170 was positively correlated to positive, but not negative, symptoms of schizophrenia. Finally, the amplitude of P100 was also decreased, which suggests that the N170 decrement would result from a more global deficit in visual processing deficit. DISCUSSION: It is suggested that, in schizophrenics, an involvement of early visual processing might underlie the decreased amplitudes and the higher onset latencies of later P300 and N400 components.

Event-related potentials (ERPs) in ecstasy (MDMA) users during a visual oddball task.

Ecstasy is the common name for a drug mainly containing a substance identified as 3,4-methylenedioxymethamphetamine (MDMA). It has become popular with participants in "raves", because it enhances energy, endurance and sexual arousal, together with the widespread belief that MDMA is a safe drug [Byard, R.W., Gilbert, J., James, R., Lokan, R.J., 1998. Amphetamine derivative fatalities in South Australia. Is "ecstasy" the culprit? Am. J. Forensic Med. Pathol. 19, 261-265]. However, it is suggested that this drug causes a neurotoxicity to the serotonergic system that could lead to permanent physical and cognitive problems. In order to investigate this issue, and during an ERP recording with 32 channels, we used a visual oddball design, in which subjects (14 MDMA abusers and 14 paired normal controls) saw frequent stimuli (neutral faces) while they had to detect as quickly as possible rare stimuli with happy or fearful expression. At a behavioral level, MDMA users imply longer latencies than normal controls to detect rare stimuli. At the neurophysiological level, ERP data suggest as main result that the N200 component, which is involved in attention orienting associated to the detection of stimulus novelty (e.g. [Campanella, S., Gaspard, C., Debatisse, D., Bruyer, R., Crommelinck, M., Guerit, J.M., 2002. Discrimination of emotional facial expression in a visual oddball task: an ERP study. Biol. Psychol. 59, 171-186]), shows shorter latencies for fearful rare stimuli (as compared to happy ones), but only for normal controls. This absence of delay was interpreted as an attentional deficit due to MDMA consumption.

Personality profile and drug of choice; a multivariate analysis using Cloninger's TCI on heroin addicts, alcoholics, and a random population group.

As personality may predispose, precipitate or perpetuate substance abuse and/or dependence, and as it is considered to remain stable across the years in a given subject, potential links with the drug of choice may help screen future patients before drug consumption. The present study compared three groups: 42 patients with heroin dependence (mean age: 31.2; standard deviation (SD): 5.5; 10 females), 37 patients with alcohol dependence (mean age 44.2; SD: 9.1; 9 females) and 83 subjects from a random population sample (mean age: 38.8; SD: 6.9; 20 females). Personality was measured by Cloninger's Temperament and Character Inventory (TCI). Pillai's MANCOVA with age as a covariate and gender as a cofactor was highly significant. Univariate ANOVA analyses using TCI dimensions as dependent variable showed most variables to vary in parallel for the two patient groups in comparison with controls. Post-hoc tests showed heroin patients to score higher in Novelty-Seeking and Self-Directedness than alcohol patients. Sub-dimensions Exploratory Excitability, Fear of the Uncertain, Responsibility, Congruent Second Nature and Transpersonal Identification were also significantly different in the two patient samples. Logistic regression showed Exploratory Excitability to segregate up to 76% of heroin patients from alcohol patients. In conclusion, personality profiles were linked to some preferential choice of drug and personality screening might be tested in preventive strategies.

Implantes de naltrexona: un avance terapéutico, tanto comportamental como farmacológico / Naltrexone implants: a real therapeutic avance both behavioural as well as pharmacological

A principios de los setenta, los pioneros del tratamiento con naltrexona (NTX) comprendieron que un implante o inyección depot de NTX ayudaría a eliminar el bajo seguimiento del tratamiento. Los primeros estudios en animales sobre formulaciones implantables aparecieron a mediados de los setenta, y los estudios en humanos pronto demostraron que los niveles efectivos de NTX en plasma podían mantenerse varias semanas con formulaciones implantables estándar. Pero sólo en los últimos años han podido emplearse implantes y depots para uso clínico. Un número creciente de artículos describen su efectividad en la prevención de recaídas, incluyendo casos de médicos y embarazadas adictos y adolescentes problemáticos que consumen frecuentemente sobredosis de opiáceos. Los niveles típicos de NTX en plasma derivados de los implantes pueden bloquear completamente los efectos de los opiáceos de hasta 500 mg de heroína farmacológica durante más de seis meses. Incluso los implantes de 'primera generación', de más corto efecto, reducen considerablemente los elevados índices de temprana reincidencia comunes tras una desintoxicación de opiáceos. Los depots de NTX tienen también potencial en los tratamientos del alcoholismo. Pero la naturaleza farmacológica de los implantes de NTX no debe ocultar que también facilitan y refuerzan importantes procesos psicológicos cruciales en el éxito a largo plazo de los tratamientos de adicción. El desarrollo de agentes bloqueadores de larga duración para otras drogas de consumo significa que los nuevos principios de los tratamientos con implantes de NTX podrán aplicarse pronto a problemas relacionados con benzodiacepinas, estimulantes y cannabis. Recomendamos el término 'abstinencia antagonista-asistida' para este enfoque, pero insistimos en que los tratamientos de mantenimiento siguen ocupando un importante lugar (AU)

The pioneers of naltrexone (NTX) treatment the early 1970s realized that an implant or depot injection of NTX would largely eliminate the poor compliance that undermined its potential effectiveness. Animal studies of implantable formulations appeared in the mid-1970s and human studies soon showed that effective plasma NTX levels could be maintained for several weeks using standard implant formulations. Yet only in the past few years have implants and depot injections become available for clinical use. This paper reviews their development, their rationale and the increasing number of papers describing their effectiveness for relapse prevention in a surprisingly wide range of indications, including addicted physicians, pregnant addicts and troubled adolescents taking frequent opiate overdoses. It is clear that typical plasma levels of NTX from implants can completely block opiate effects from as much as 500 mg of pharmaceutical heroin and effective blockade can be maintained for well over six months. Even shorteracting 'first generation' implants appear to reduce considerably the high rates of early relapse that are common after opiate detoxification. Depot NTX also has potential in alcoholism treatment. However, the obviously pharmacological nature of NTX implants should not obscure the fact that they also facilitate and reinforce important psychological processes that may be crucial to the long-term success of addiction treatment. The development of long-acting blocking agents for other drugs of abuse means that the emerging principles of treatment with NTX implants may soon be applied to problems involving benzodiazepines, stimulants and cannabis. We suggest the term 'Antagonist-Assisted Abstinence' for this approach but stress that maintenance treatments continue to have an important place (AU)

Deficits in recognition of emotional facial expression are still present in alcoholics after mid- to long-term abstinence.

OBJECTIVE: Emotional facial expression (EFE) decoding skills play a key role in interpersonal relationships. Decoding errors have been described in several pathological conditions, including alcoholism. The aim of this study was to investigate whether EFE decoding skill deficits persist after abstention from alcohol of at least 2 months. METHOD: Alcoholic patients abstinent for at least 2 months (n = 25) were compared with 25 recently detoxified patients and with 25 normal controls matched for age, gender and educational level. Subjects were presented with 40 photographs of facial expressions portraying happiness, anger, sadness, disgust and fear. Each emotion was displayed with neutral, mild, moderate and strong emotional intensity. Each facial expression was judged successively on eight scales labeled happiness, sadness, fear, anger, disgust, surprise, shame and contempt. For each scale, subjects rated the estimated intensity level. A complementary scale assessed the self-estimated difficulty in performing the task. RESULTS: Recently detoxified alcoholics were significantly less accurate than controls, making more EFE labeling errors and overestimating the intensity of the portrayed emotions. Deficits in decoding accuracy for anger and disgust were present in mid- to long-term abstinent patients; intensity overestimation was present in the former and absent in the latter. CONCLUSIONS: Deficits in decoding accuracy for anger and disgust, and to a lesser degree sadness, persist with an abstinence of 2 months and beyond. Right frontotemporal regions and cingulate could be implicated. These deficits may contribute to the social skills deficits frequently encountered in alcoholic patients.

Occipital activation by pattern recognition in the early blind using auditory substitution for vision.

This PET study aimed at investigating the neural structures involved in pattern recognition in early blind subjects using sensory substitution equipment (SSE). Six early blind and six blindfolded sighted subjects were studied during three auditory processing tasks: a detection task with noise stimuli, a detection task with familiar sounds, and a pattern recognition task using the SSE. The results showed a differential activation pattern with the SSE as a function of the visual experience: in addition to the regions involved in the recognition process in sighted control subjects, occipital areas of early blind subjects were also activated. The occipital activation was more important when the early blind subjects used SSE than during the other auditory tasks. These results suggest that activity of the extrastriate visual cortex of early blind subjects can be modulated and bring additional evidence that early visual deprivation leads to cross-modal cerebral reorganization.

Interference with withdrawal signs of naloxone-induced opiate withdrawal under anesthesia is anesthetic-specific in opiate-dependent rats.

We hypothesized that interference of opiate antagonist-precipitated withdrawal signs under anesthesia is anesthetic-specific. Three groups of morphine-dependent rats were compared in different experimental conditions using a protocol of rapid withdrawal induction by an antagonist under anesthesia. We observed that ketamine and midazolam have different effects on the expression of withdrawal. This brings specific insights into the pharmacological basis of therapy with induction of opiate antagonist.

Previous anesthesia can temporarily overshadow the expression of a withdrawal syndrome in opiate dependent rats.

We hypothesized that induction of opiate antagonist-precipitated withdrawal under anesthesia can decrease the expression of later withdrawal signs. Three groups of morphine-dependent rats were compared in different experimental conditions of withdrawal precipitation using naloxone. We showed that anesthesia can temporarily overshadow the expression of withdrawal signs, but that some signs can be delayed and increased in intensity. This can be explained by a parallel and temporary effect of anesthesia on arousal and pain threshold. This carries important implications on the use of anesthesia in detoxification procedures.

Alcoholics' deficits in the decoding of emotional facial expression.

The present study investigated emotional facial expression decoding in alcoholics. Twenty-five alcoholic patients at the end of the detoxification process were compared with 25 volunteers matched for age, sex, and education. They were presented with facial expressions of neutral, mild, moderate, or strong emotional intensity. Results indicate that alcoholics overestimate the intensity of emotional expressions and make more errors in their decoding with a special bias for anger and contempt. Moreover, this decoding deficit is not perceived by the alcoholic patients. A general model is proposed that links visuospatial deficits, abnormal processing of social information, interpersonal stress, and alcohol abuse.