The Broad Autism Phenotype-International Test (BAP-IT): A two-domain-based test for the assessment of the broad autism phenotype.

LAY ABSTRACT: The broad autism phenotype refers to a group of behaviors related to autism spectrum disorder, but that appear to a lesser extent. Its assessment has been performed through outdated broad autism phenotype/autism spectrum disorder definitions and tests. To address this problem, this study presents the development of a new test, the Broad Autism Phenotype-International Test, a 20-item measure consisting of two dimensions, SOCIAL-BAP and RIRE-BAP, targeting the two-domain operationalization of autism spectrum disorder in Spain and the United Kingdom. Unlike the Broad Autism Phenotype Questionnaire, this test received empirical support as a quick and effective broad autism phenotype measure that can facilitate both broad autism phenotype/autism spectrum disorder research and interventions. This is the first step to studying the BAP in several Spanish and English-speaking countries.

Centromeric AA motif in KIR as an optimal surrogate marker for precision definition of alloimmune reproductive failure.

Throughout pregnancy, the decidua is predominantly populated by NK lymphocytes expressing Killer immunoglobulin-like receptors (KIR) that recognize human leukocyte antigen-C (HLA-C) ligands from trophoblast cells. This study aims to investigate the association of KIR-HLA-C phenotypes in couples facing infertility, particularly recurrent pregnancy loss (RPL) and recurrent implantation failure (RIF), in comparison to a reference population and fertile controls. This observational, non-interventional retrospective case-control study included patients consecutively referred to our Reproductive Immunology Unit from 2015 to 2019. We analyzed the frequencies of KIR and HLA-C genes. As control groups, we analyzed a reference Spanish population for KIR analysis and 29 fertile controls and their male partners for KIR and HLA-C combinations. We studied 397 consecutively referred women with infertility and their male partners. Among women with unexplained RPL (133 women) and RIF (176 women), the centromeric (cen)AA KIR genotype was significantly more prevalent compared to the reference Spanish population (p = 0.001 and 0.02, respectively). Furthermore, cenAA was associated with a 1.51-fold risk of RPL and a 1.2-fold risk of RIF. Conversely, the presence of BB KIR showed a lower risk of reproductive failure compared to non-BB KIR (OR: 0.12, p < 0.001). Women and their partners with HLA-C1C1/C1C1 were significantly less common in the RPL-Group (p < 0.001) and RIF-Group (p = 0.002) compared to the control group. Moreover, the combination of cenAA/C1C1 in women with C1C1 partners was significantly higher in the control group than in the RPL (p = 0.009) and RIF (p = 0.04) groups, associated with a 5-fold increase in successful pregnancy outcomes. In our cohort, the cenAA KIR haplotype proved to be a more accurate biomarker than the classic AA KIR haplotype for assessing the risk of RPL and RIF, and might be particularly useful to identify women at increased risk among the heterogeneous KIR AB or Bx population. The classification of centromeric KIR haplotypes outperforms classical KIR haplotypes, making it a better indicator of potential maternal-fetal KIR-HLA-C mismatch in patients.

The role of the differential outcomes procedure and schizotypy in the recognition of dynamic facial expressions of emotions.

Emotional facial expression recognition is a key ability for adequate social functioning. The current study aims to test if the differential outcomes procedure (DOP) may improve the recognition of dynamic facial expressions of emotions and to further explore whether schizotypal personality traits may have any effect on performance. 183 undergraduate students completed a task where a face morphed from a neutral expression to one of the six basic emotions at full intensity over 10 s. Participants had to press spacebar as soon as they identified the emotion and choose which had appeared. In the first block, participants received no outcomes. In the second block, a group received specific outcomes associated to each emotion (DOP group), while another group received non-differential outcomes after correctly responding (NOP group). Employing generalized linear models (GLMs) and Bayesian inference we estimated different parameters to answer our research goals. Schizotypal personality traits did not seem to affect dynamic emotional facial expression recognition. Participants of the DOP group were less likely to respond incorrectly to faces showing Fear and Surprise at fewer intensity levels. This may suggest that the DOP could lead to better identification of the main features that differentiate each facial expression of emotion.

Mental rotation and schizotypal personality traits: A Bayesian approach.

People diagnosed with schizophrenia exhibit mental rotation differences, suggesting that clinical levels of positive symptoms, such as psychotic hallucinations, are related to disruptions in their monitoring and manipulation of mental representations. According to the psychosis continuum, findings in people with a high level of schizotypal personality traits are expected to be qualitatively similar, but research concerning this topic is scarce. A spared mental imagery manipulation in this population only could suggest that this ability might be a possible protective factor, or that the emergence of clinical-level positive symptoms could be paired with disruptions in this capacity. To explore this issue, 205 undergraduate students (122 women) completed a novel mental rotation task identifying the stimulus that was a 90, 180, or 270° rotation of a black circle with colored portions and were assessed with the Schizotypal Personality Questionnaire. Men performed better in most conditions. No relationship was detected between schizotypal personality traits and accuracy in the task. These results do not support that mental imagery manipulation disruptions may be related to schizotypal personality traits in non-clinical populations. Thus, they might instead be associated with the onset of psychosis disorders as mental representation handling is hindered. However, additional research is required including the general population, as well as those with higher levels of psychotic symptoms and psychosis disorders. Future research could also focus on working memory processes related to mental representation manipulations of different sensory modalities such as auditory mental representations and their relationship with schizotypal personality traits and clinical populations.

Schizotypal personality traits and the social learning of fear.

Schizotypy can be defined as a combination of traits qualitatively similar to those found in schizophrenia, but milder in their expression, that can be found in clinical and non-clinical populations. In this research, we explore, to our knowledge, for the first time, whether schizotypal personality traits may affect the acquisition of conditioned fear by social means only. Apart from being an essential capacity to ensure learning in safe environments, social fear learning shares important characteristics with direct fear acquisition, which also makes it a great candidate for developing successful extinction procedures. Undergraduate students (n = 72) performed a task of social fear learning. In this task, participants watched a video of a person that simulated to receive electric shocks (unconditioned stimulus; US) paired with a coloured square (conditioned stimulus plus; CS+), while another coloured square was never paired (conditioned stimulus minus; CS-) with the shock. After that, they were presented with a similar sequence of coloured screens. Their Skin Conductance Responses (SCRs) were registered during the whole process. Once they finished, they completed the Schizotypal Personality Questionnaire (SPQ). Our results revealed that participants with a low score in the Cognitive-Perceptual factor of the SPQ exhibited higher SCRs when they saw the US than when they saw the CS- (all ps < 0.01) during the learning phase. Nevertheless, those with higher scores did not present any difference in their SCRs toward both stimuli (all ps > 0.05), a pattern that has been similarly found in schizophrenia. During the final trials of the test phase, participants with the highest scores in the Disorganized factor were the only ones that maintained a higher SCR towards the CS+ than towards the CS- (p = 0.006), which could be associated with an impairment in their extinction processes.

The Effect of Multiprobiotics on Memory and Attention in Fibromyalgia: A Pilot Randomized Controlled Trial.

Fibromyalgia syndrome (FMS) is a chronic, generalized and diffuse pain disorder accompanied by cognitive deficits such as forgetfulness, concentration difficulties, loss of vocabulary and mental slowness, among others. In recent years, FMS has been associated with altered intestinal microbiota, suggesting that modulating gut microbiota (for example, through probiotics) could be an effective therapeutic treatment. Thus, the aim of the present study was to continue exploring the role of probiotics in cognitive processes in patients with FMS. A pilot randomized controlled trial was conducted in 31 patients diagnosed with FMS to compare the effects of a multispecies probiotic versus a placebo on cognitive variables (memory and attention) after eight weeks. Results showed that treatment with a multispecies probiotic produced an improvement in attention by reducing errors on an attention task, but it had no effect on memory. More specifically, a tendency to reduce errors of omission (Go trials) during the Go/No-Go Task was observed after treatment. These findings, along with our previous results in impulsivity, underline the relevance of using probiotics as a therapeutic option in FMS, although more research with a larger sample size is required.

Differential outcomes, schizotypy, and improvement of the recognition of emotional facial expressions: a preliminary study

Schizotypy is defined as a combination of traits qualitatively similar to those found in schizophrenia, though in a minor severity, that can be found in the nonclinical population. Some studies suggest that people with schizotypal traits have problems recognising emotional facial expressions. In this research, we further explore this issue and we investigate, for the first time, whether the differential outcomes procedure (DOP) may improve the recognition of emotional facial expressions. Participants in our study were students that completed the ESQUIZO-Q-A and were set in two groups, high schizotypy (HS) and low schizotypy (LS). Then, they performed a task in which they had to recognise the emotional facial expression of a set of faces. Participants of the HS group and the LS group did not differ in their performance. Importantly, all participants showed better recognition of emotional facial expressions when they were trained with differential outcomes. This novel finding might be relevant for clinical practice since the DOP is shown as a tool that may improve the recognition of emotional facial expressions

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A Pilot Randomized Controlled Trial to Explore Cognitive and Emotional Effects of Probiotics in Fibromyalgia.

It has recently been found that microbes in the gut may regulate brain processes through the gut microbiota-brain axis, which modulates affection, motivation and higher cognitive functions. According to this finding, the use of probiotics may be a potential treatment to improve physical, psychological and cognitive status in clinical populations with altered microbiota balance such as those with fibromyalgia (FMS). Thus, the aim of the present pilot study with a double-blind, placebo-controlled, randomised design was to test whether a multispecies probiotic may improve cognition, emotional symptoms and functional state in a sample of patients diagnosed with FMS. Pain, impact of FMS, quality of life, anxiety and depressive symptoms were measured during the pre- and post-intervention phases; participants also completed two computerised cognitive tasks to assess impulsive choice and decision-making. Finally, urinary cortisol concentration was determined. To our knowledge, this is the first study that explore the effect of a multispecies probiotic in FMS patients. Our results indicated that probiotics improved impulsivity and decision-making in these patients. However, more research is needed to further explore the potential effects of probiotics on other cognitive functions affected in FMS as well as in other clinical populations.

Psychometric Properties of the Spanish Version of the Broad Autism Phenotype Questionnaire: Strengths, Weaknesses, and Future Improvements.

The Broad autism phenotype (BAP) refers to a set of subclinical behavioural characteristics qualitatively similar to those presented in Autism spectrum disorders (ASDs). The BAP questionnaire (BAPQ) has been widely used to assess the BAP both in relatives of ASD people and within the general population. The current study presents the first Spanish version of the BAPQ (BAPQ-SP) and analyses its psychometric properties, including validity evidences based on the BAPQ scores relationship with other variables. Our results only support the use of the Aloof and Rigid sub-scales to assess this phenotype, whereas Pragmatic Language sub-scale seems to be the main source of misfit. This research represents a first step in the study of the BAP features in the Spanish population.

In vivo stimulation of locus coeruleus: effects on amygdala subnuclei.

The locus coeruleus (LC) is the major noradrenergic nucleus and sends projections to almost all brain areas. A marked increase in norepinephrine release has been demonstrated in several brain areas in response to exposure to acute stressful stimuli, especially those innervated by LC projections. One of the brain areas innervated by LC neurons is the amygdala, a structure highly involved in emotional processes and memory formation. The aim of this study was to increase knowledge of the functional connectivity between the LC and the amygdala subnuclei. To reach this objective, we evaluated c-fos immunoreactive cells in amygdala nuclei following direct electrical stimulation of the LC in conscious animals. This analysis of c-Fos immunoreactivity could inform whether there are differences in activity of the amygdala subnuclei related to LC electrical stimulation in conscious animals. Our results showed a marked increase in c-fos activity in these amygdala subnuclei both ipsilateral and contralateral to LC electrical stimulation in vivo. Therefore, our study provides evidence that in vivo electrical stimulation of LC is able to activate the amygdala subnuclei as measured by c-fos expression.

Probiotics for fibromyalgia: study design for a pilot double-blind, randomized controlled trial.

BACKGROUND: Fibromyalgia syndrome (FMS) is a chronic, generalized and diffuse pain disorder accompanied by other symptoms such as emotional and cognitive deficits. The FMS patients show a high prevalence of gastrointestinal symptoms. Recently it has been found that microbes in the gut may regulate brain processes through the gut-microbiota-brain axis, modulating thus affection, motivation and higher cognitive functions. Therefore, the use of probiotics might be a new treatment that could improve the physical, psychological and cognitive state in FMS; however, no evidence about this issue is available. METHODS: This paper describes the design and protocol of a double-blind, placebo-controlled and randomized pilot study. We use validated questionnaires, cognitive task through E-Prime and biological measures like urine cortisol and stool fecal samples. The trial aim is to explore the effects of eight weeks of probiotics therapy in physical (pain, impact of the FMS and quality of life), emotional (depression, and anxiety) and cognitive symptoms (attention, memory, and impulsivity) in FMS patients as compared to placebo. CONCLUSION: This pilot study is the first, to our knowledge, to evaluate the effects of probiotics in FMS. The primary hypothesis was that FMS patients will show a better performance on cognitive tasks, and an improvement in emotional and physical symptoms. These results will contribute to a better understanding in the gut-brain axis. Here we present the design and protocol of the study.

Probiotics for fibromyalgia: study design for a pilot double-blind, randomized controlled trial / Probióticos en fibromialgia: diseño de un estudio piloto doble ciego y randomizado

Background: Fibromyalgia syndrome (FMS) is a chronic, generalized and diffuse pain disorder accompanied by other symptoms such as emotional and cognitive deficits. The FMS patients show a high prevalence of gastrointestinal symptoms. Recently it has been found that microbes in the gut may regulate brain processes through the gut-microbiota-brain axis, modulating thus affection, motivation and higher cognitive functions. Therefore, the use of probiotics might be a new treatment that could improve the physical, psychological and cognitive state in FMS; however, no evidence about this issue is available. Methods: This paper describes the design and protocol of a double-blind, placebo-controlled and randomized pilot study. We use validated questionnaires, cognitive task through E-Prime and biological measures like urine cortisol and stool fecal samples. The trial aim is to explore the effects of eight weeks of probiotics therapy in physical (pain, impact of the FMS and quality of life), emotional (depression, and anxiety) and cognitive symptoms (attention, memory, and impulsivity) in FMS patients as compared to placebo. Conclusion: This pilot study is the first, to our knowledge, to evaluate the effects of probiotics in FMS. The primary hypothesis was that FMS patients will show a better performance on cognitive tasks, and an improvement in emotional and physical symptoms. These results will contribute to a better understanding in the gut-brain axis. Here we present the design and protocol of the study (AU)

Antecedentes: el síndrome de fibromialgia (FMS) es un trastorno crónico, generalizado y difuso que produce dolor acompañado de otros síntomas emocionales y cognitivos. Así mismo, los pacientes con FMS muestran una alta comorbilidad de síntomas gastrointestinales. En este sentido, recientemente se ha encontrado que la microbiota intestinal es capaz de regular procesos cerebrales a través del eje intestino-microbiota-cerebro, modulando así a nivel afectivo, emocional, motivacional y de funciones cognitivas complejas. Por lo tanto, el uso de probióticos podría ser una nueva estrategia terapéutica para mejorar el estado físico, psicológico y cognitivo en pacientes con FMS. Sin embargo, aún no hay evidencia disponible sobre este tema. Métodos: este artículo describe el diseño y el protocolo de un estudio piloto doble ciego, controlado con placebo y aleatorizado. Se utilizan cuestionarios validados, tareas cognitivas a través de E-Prime y medidas biológicas como cortisol de orina y muestras de heces. El objetivo del estudio es explorar el efecto de un tratamiento multiespecies probióticas durante ocho semanas en la sintomatología física (dolor, impacto del FMS y calidad de vida), emocional (depresión y ansiedad) y cognitiva (atención, memoria e impulsividad) en pacientes con FMS. Conclusión: el protocolo de este estudio piloto, a nuestro conocer, es el primero que pretende evaluar los efectos de los probióticos en FMS. La hipótesis de partida es que los pacientes con FMS mostrarán un mejor desempeño en las tareas cognitivas y una mejoría en los síntomas emocionales y físicos. Estos resultados contribuirán a una mejor comprensión del eje intestino-cerebral (AU)

Comparative study on short- and long-term behavioral consequences of organophosphate exposure: relationship to AChE mRNA expression.

Organophosphates (OPs) affect behavior by inhibiting acetylcholinesterase (AChE). While the cognitive short-term effects may be directly attributed to this inhibition, the mechanisms that underlie OP's long-term cognitive effects remain controversial and poorly understood. Accordingly, two experiments were designed to assess the effects of OPs on cognition, and to ascertain whether both the short- and long-term effects of are AChE-dependent. A single subcutaneous dose of 250 mg/kg chlorpyrifos (CPF), 1.5mg/kg diisopropylphosphorofluoridate (DFP) or 15 mg/kg parathion (PTN) was administered to male Wistar rats. Spatial learning was evaluated 72 h or 23 weeks after exposure, and impulsive choice was tested at 10 and 30 weeks following OPs administration (experiment 1 and 2, respectively). Brain soluble and membrane-bound AChE activity, synaptic AChE-S mRNA, read-through AChE-R mRNA and brain acylpeptide hydrolase (APH) activity (as alternative non-cholinergic target) were analyzed upon completion of the behavioral testing (17 and 37 weeks after OPs exposure). Both short- and long-term CPF treatment caused statistically significant effects on spatial learning, while PTN treatment led only to statistically significant short-term effects. Neither CPF, DFP nor PTN affected the long-term impulsivity response. Long-term exposure to CPF and DFP significantly decreased AChE-S and AChE-R mRNA, while in the PTN treated group only AChE-S mRNA levels were decreased. However, after long-term OP exposure, soluble and membrane-bound AChE activity was indistinguishable from controls. Finally, no changes were noted in brain APH activity in response to OP treatment. Taken together, this study demonstrates long-term effects of OPs on AChE-S and AChE-R mRNA in the absence of changes in AChE soluble and membrane-bound activity. Thus, changes in AChE mRNA expression imply non-catalytic properties of the AChE enzyme.

Chronic dietary exposure to chlorpyrifos causes behavioral impairments, low activity of brain membrane-bound acetylcholinesterase, and increased brain acetylcholinesterase-R mRNA.

Chlorpyrifos (CPF) is an organophosphate (OP) insecticide that is metabolically activated to the highly toxic chlorpyrifos oxon. Dietary exposure is the main route of intoxication for non-occupational exposures. However, only limited behavioral effects of chronic dietary exposure have been investigated. Therefore, male Wistar rats were fed a dose of 5mg/kg/day of CPF for thirty-one weeks. Animals were evaluated in spatial learning and impulsivity tasks after 21 weeks of CPF dietary exposure and one week after exposure ended, respectively. In addition, the degree of inhibition of brain acetylcholinesterase (AChE) was evaluated for both the soluble and particulate forms of the enzyme, as well as AChE gene expression. Also, brain acylpeptide hydrolase (APH) was investigated as an alternative target for OP-mediated effects. All variables were evaluated at various time points in response to CPF diet and after exposure ended. Results from behavioral procedures suggest cognitive and emotional disorders. Moreover, low levels of activity representing membrane-bound oligomeric forms (tetramers) were also observed. In addition, increased brain AChE-R mRNA levels were detected after four weeks of CPF dietary exposure. However, no changes in levels of brain APH were observed among groups. In conclusion, our data point to a relationship between cognitive impairments and changes in AChE forms, specifically to a high inhibition of the particulate form and a modification of alternative splicing of mRNA during CPF dietary exposure.

Dose-dependent regional brain acetylcholinesterase and acylpeptide hydrolase inhibition without cell death after chlorpyrifos administration.

Organophosphates (OPs) are important toxic compounds commonly used for a variety of purposes in agriculture, industry and household settings. It has been well established that the main mechanism of acute toxic action of OP is the inhibition of acetylcholinesterase (AChE). However, we observed long term deficit after acute subcutaneous exposure to Chlorpyrifos (CPF) even when AChE activity is restored. In fact, besides AChE inhibition, non-AChE targets have also been proposed as an alternative mechanism involved in the acute lethal action and side effects of short or long-term exposure. In this context, our main aim in this research was to establish a dose-response curve of Acylpeptide hydrolase (APH) and AChE regional brain activity after acute CPF administration that could explain these long term effects observed in the literature. Moreover, since available data suggest that long term effects of OPs exposure could involve neuronal cell death, our second aim was to evaluate, assessing by Fluoro-Jade B (FJB) staining, whether CPF produces induced cell death. Our results show that an acute exposure to 250 mg/kg CPF does not induce neuronal death as measured by FJB but produces highest AChE regional brain inhibition after administration. In addition, APH seems to be more sensitive than AChE to CPF exposure because after 31 days of exposure, complete recovery was seen only for APH activity at Frontal Cortex, Cerebellum and Brain Stem.

Chlorpyrifos-, diisopropylphosphorofluoridate-, and parathion-induced behavioral and oxidative stress effects: are they mediated by analogous mechanisms of action?

Exposure to organophosphates (OPs) can lead to cognitive deficits and oxidative damage. Little is known about the relationship between behavioral deficits and oxidative stress within the context of such exposures. Accordingly, the first experiment was carried out to address this issue. Male Wistar rats were administered 250 mg/kg of chlorpyrifos (CPF), 1.5 mg/kg of diisopropylphosphorofluoridate (DFP), or 15 mg/kg of parathion (PTN). Spatial learning in the water maze task was evaluated, and F(2)-isoprostanes (F(2)-IsoPs) and prostaglandin (PGE(2)) were analyzed in the hippocampus. A second experiment was designed to determine the degree of inhibition of brain acetylcholinesterase (AChE) activity, both the soluble and particulate forms of the enzyme, and to assess changes in AChE gene expression given evidence on alternative splicing of the gene in response to OP exposures. In addition, brain acylpeptide hydrolase (APH) activity was evaluated as a second target for OP-mediated effects. In both experiments, rats were sacrificed at various points to determine the time course of OPs toxicity in relation to their mechanism of action. Results from the first experiment suggest cognitive and emotional deficits after OPs exposure, which could be due to, at least in part, increased F(2)-IsoPs levels. Results from the second experiment revealed inhibition of brain AChE and APH activity at various time points post OP exposure. In addition, we observed increased brain read-through splice variant AChE (AChE-R) mRNA levels after 48 h PTN exposure. In conclusion, this study provides novel data on the relationship between cognitive alterations and oxidative stress, and the diverse mechanisms of action along a temporal axis in response to OP exposures in the rat.

Discriminative stimulus properties of naloxone in Long-Evans rats: assessment with the conditioned taste aversion baseline of drug discrimination learning.

RATIONALE: The characterization of the discriminative stimulus properties of naloxone has focused primarily on its actions at the mu opioid receptor, although naloxone also displays an affinity for delta and kappa receptor subtypes. OBJECTIVES: The present study extends this characterization of the naloxone cue by investigating if relatively specific antagonists for the mu (naltrexone: 0.10-0.56 mg/kg), delta (naltrindole: 1-18 mg/kg), and kappa (MR2266: 1.8-10 mg/kg) opioid receptor subtypes will substitute for naloxone in animals trained to discriminate naloxone from its vehicle. The temporal nature of the naloxone cue was examined by varying pretreatment time points (15, 30, 45, 60 min). Finally, various doses of naltrexone methobromide (1-18 mg/kg) were assessed to determine peripheral mediation of the cue. MATERIALS AND METHODS: Female Long-Evans rats (N = 30) received an injection of naloxone (1 mg/kg; i.p.) 15 min prior to a pairing of saccharin (20-min access) and the emetic LiCl (1.8 mEq; i.p.; n = 16, group NL) or vehicle (n = 14, group NW); on other days, they were injected with saline prior to saccharin alone. Substitution tests with compounds with various receptor affinities and selective CNS and PNS actions were then assessed. RESULTS: Only naloxone and naltrexone produced dose-dependent decreases in saccharin consumption. Naloxone administered at 15 and 30 min before saccharin produced decreases in consumption similar to that displayed on training days. Naltrexone methobromide substituted only at the highest dose tested (18 mg/kg). CONCLUSIONS: Naloxone's stimulus effects appear to be mediated centrally via activity at the mu opioid receptor.

Long-term monoamine changes in the striatum and nucleus accumbens after acute chlorpyrifos exposure.

This study examined the time-course effects (2, 7, 14 and 30 days) of acute chlorpyrifos (CPF) intoxication (250 mg/kg, s.c.) on monoamine systems and acetylcholinesterase (AChE) activity in the striatum and nucleus accumbens of adult male rats. We show that CPF produced significant long-term inhibition of AChE activity in the striatum and nucleus accumbens. In the striatum, CPF intoxication resulted in changes in dopamine (DA) metabolism after 2 days and changes in serotonin (5-HT) turnover after 7 and 15 days. Significant decreases in monoamine content including norepinephrine (NE), DA, 5-HT and their metabolites were found in the nucleus accumbens 30 days after CPF intoxication. These results suggest that acute exposure to CPF induces long-term changes in the monoamine systems (NE, DA and 5-HT) in adult animals. The lack of correlation between regional AChE activity and neurochemical outcomes points to independent mechanisms.

Long-term neurotoxicity of chlorpyrifos: spatial learning impairment on repeated acquisition in a water maze.

Organophosphate compounds are cholinesterase inhibitors widely used in agriculture, industry, household products, and even as chemical weapons. Their major mechanism of acute toxic action is the inhibition of acetylcholinesterase, which is responsible for the degradation of the neurotransmitter acetylcholine. An organophosphorus ester-induced chronic neurotoxicity (OPICN) syndrome has been proposed. The OPICN syndrome could result from both long-term exposure to subclinical doses of OPs and after acute poisoning. Development of animal models for the cognitive decline are required and could later help to elucidate the mechanisms involved in this long-term effect on the central nervous system. Previously, we have found performance decrements in a four-trial repeated acquisition spatial task in a water maze. The present study includes two experiments to extend the long-term behavioral effects observed. Rats were injected either once or twice with chlorpyrifos (CPF) and then tested months after in a two-trial repeated acquisition task in a water maze. Our results confirm and extend the long-term behavioral effects of subcutaneous administration of CPF. The two treatments used produced performance decrements that suggest functional central nervous system alterations.

Long-term functional neurotoxicity of paraoxon and chlorpyrifos: behavioural and pharmacological evidence.

Organophosphate (OP) compounds are chemicals widely used in agriculture, industry and households and even as chemical weapons. The major mechanism of acute toxic action is the inhibition of acetylcholinesterase (AChE), which is responsible for the degradation of the neurotransmitter acetylcholine. A chronic OP-induced neuropsychiatric disorder (COPIND), which could result from both long-term exposure to subclinical doses of OP and after acute intoxication, has been proposed. These reports claim to develop animal models that could parallel behavioural and cognitive effects and that could later help to elucidate the mechanisms involved in this long-term affectation of the central nervous system. The present study uses a series of behavioural tests to discern the short- and long-term effects of acute intoxications with paraoxon (Px) or chlorpyrifos (CPF). Our results suggest that months after acute exposure to these OPs functional central nervous system alterations can be detected using a repeated acquisition spatial task in the water maze, for CPF, and in amphetamine-induced place preference paradigm, for both Px and CPF.