Baricitinib or imatinib in hospitalized COVID-19 patients: Results from COVINIB, an exploratory randomized clinical trial.

Baricitinib and imatinib are considered therapies for coronavirus disease 2019 (COVID-19), but their ultimate clinical impact remains to be elucidated, so our objective is to determine whether these kinase inhibitors provide benefit when added to standard care in hospitalized COVID-19 patients. Phase-2, open-label, randomized trial with a pick-the-winner design conducted from September 2020 to June 2021 in a single Spanish center. Hospitalized adults with COVID-19 pneumonia and a symptom duration ≤10 days were assigned to 3 arms: imatinib (400 mg qd, 7 days) plus standard-care, baricitinib (4 mg qd, 7 days) plus standard-care, or standard-care alone. Primary outcome was time to clinical improvement (discharge alive or a reduction of 2 points in an ordinal scale of clinical status) compared on a day-by-day basis to identify differences ≥15% between the most and least favorable groups. Secondary outcomes included oxygenation and ventilatory support requirements, additional therapies administered, all-cause mortality, and safety. One hundred and sixty-five patients analyzed. Predefined criteria for selection of the most advantageous arm were met for baricitinib, but not for imatinib. However, no statistically significant differences were observed in formal analysis, but a trend toward better results in patients receiving baricitinib was found compared to standard care alone (hazard ratio [HR] for clinical improvement: 1.41, 95% confidence intervals [CI]: 0.96-2.06; HR for discontinuing oxygen: 1.46, 95% CI: 0.94-2.28). No differences were found regarding additional therapies administered or safety. Baricitinib plus standard care showed better results for hospitalized COVID-19 patients, being the most advantageous therapeutic strategy among those proposed in this exploratory clinical trial.

Correction to: Mind, Brain, and Behavior: an Integrative Approach to Teaching Neuroscience to Medical Students.

This article was updated to correct Ignacio Martinez Escobedo's name.

Distinct dendritic morphology across the blades of the rodent dentate gyrus.

The dentate gyrus (DG) is a hippocampal region that has long been characterized as a critical mediator of enduring memory formation and retrieval. As such, there is a wealth of studies investigating this area. Most of these studies have either treated the DG as a homogeneous structure, or examined differences in neurons along the septal-temporal axis. Recent data, however, have indicated that a functional distinction exists between the suprapyramidal and infrapyramidal blades of the DG, with the former showing more robust responses during spatial tasks. To date, few anatomical studies have addressed this functional gradient in rats, and no study has done so in the mouse. To address this, we investigated dendritic morphology and spine density in hippocampal granule cells of rats and mice using the Golgi-Cox technique. We find that granule cells from the suprapyramidal blade of the DG contain greater dendritic material in the region receiving spatial information from the medial perforant path. This provides a potential anatomical substrate for the asymmetric response of the DG to spatial input. Synapse 70:277-282, 2016. © 2016 Wiley Periodicals, Inc.

Enriched Environment Contributes to the Recovery from Neurotoxin-Induced Parkinson's Disease Pathology.

Parkinson's disease (PD) is a neurological disorder that affects dopaminergic neurons. The lack of understanding of the underlying molecular mechanisms of PD pathology makes treating it a challenge. Several pieces of evidence support the protective role of enriched environment (EE) and exercise on dopaminergic neurons. The specific aspect(s) of neuroprotection after exposure to EE have not been identified. Therefore, we have investigated the protective role of EE on dopamine dysregulation and subsequent downregulation of DJ1 protein using in vitro and in vivo models of PD. Our study for the first time demonstrated that DJ1 expression has a direct correlation with dopamine downregulation in PD models and exposure to EE has a significant impact on improving the behavioral changes in PD mice. This research provides evidence that exercise in EE has a positive effect on PD without interfering with the current line of therapy.

Social reward: interactions with social status, social communication, aggression, and associated neural activation in the ventral tegmental area.

Nearly all species engage in a variety of intraspecific social interactions, and there is evidence that these interactions are rewarding. Less is known, however, about the factors that influence social reward. Using the conditioned place preference paradigm, we tested whether social interactions are rewarding for male Syrian hamsters. We also tested whether social stimuli increase neural activation in the ventral tegmental area (VTA), a component of the mesolimbic reward system, and how individual differences in social behavior and experience influence neural activation. In the present study, we found that hamsters developed a conditioned place preference for social interactions, but the effects were significantly stronger in dominant animals compared with subordinates. The number of Fos-immunoreactive cells in the VTA was significantly higher in hamsters that had engaged in a direct social encounter compared with hamsters exposed to a caged stimulus hamster or controls. Interestingly, socially experienced males had more Fos-immunoreactive cells in the VTA than socially naive males after exposure to a social stimulus. Surprisingly, the amount of Fos immunoreactivity in the VTA induced by a social stimulus was correlated with the amount of aggressive/dominance behaviors that had been observed during interactions that had occurred 2 months earlier. Our results indicate that social interactions between males are rewarding, and that social dominance increases the reward value. Social interactions stimulate the mesolimbic reward system, and social experience enhances its response to novel social stimuli and may produce long-term changes in the neural mechanisms that mediate the maintenance of dominance over long periods of time.

Development and Validation of a New Home Cooking Frequency Questionnaire: A Pilot Study.

Home cooking and the type of cooking techniques can have an effect on our health. However, as far as we know, there is no questionnaire that measures in depth the frequency and type of cooking techniques used at home. Our aim was to design a new Home Cooking Frequency Questionnaire (HCFQ) and to preliminarily assess its psychometric properties. For this purpose we used a five-phase approach, as follows: Phase 1: item generation based on expert opinion, relevant literature and previous surveys; Phase 2: content validity assessed by experts for relevance and clarity (epidemiologists, dietitians, chefs); Phase 3: face validity and inter-item reliability; Phase 4: criterion validity using a 7-day food and culinary record; and Phase 5: test stability and inter-item reliability. The content validity index for scale and item level values provided evidence of the content validity for relevance and clarity. Criterion validity analysis showed intraclass correlation coefficients ranged from 0.31−0.69. Test−retest reliability coefficients ranged from 0.49−0.92, with ƙ values > 0.44. Overall Cronbach's alpha was 0.90. In conclusion, the HCFQ is a promising tool with sound content and face validity, substantial criterion validity, and adequate reliability. This 174-item HCFQ is the first questionnaire to assess how often people cook and which cooking methods they use at home.

Evaluation in a Cytokine Storm Model In Vivo of the Safety and Efficacy of Intravenous Administration of PRS CK STORM (Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells).

Our research group has been developing a series of biological drugs produced by coculture techniques with M2-polarized macrophages with different primary tissue cells and/or mesenchymal stromal cells (MSC), generally from fat, to produce anti-inflammatory and anti-fibrotic effects, avoiding the overexpression of pro-inflammatory cytokines by the innate immune system at a given time. One of these products is the drug PRS CK STORM, a medium conditioned by allogenic M2-polarized macrophages, from coculture, with those macrophages M2 with MSC from fat, whose composition, in vitro safety, and efficacy we studied. In the present work, we publish the results obtained in terms of safety (pharmacodynamics and pharmacokinetics) and efficacy of the intravenous application of this biological drug in a murine model of cytokine storm associated with severe infectious processes, including those associated with COVID-19. The results demonstrate the safety and high efficacy of PRS CK STORM as an intravenous drug to prevent and treat the cytokine storm associated with infectious processes, including COVID-19.

Cytokine Profile and Anti-Inflammatory Activity of a Standardized Conditioned Medium Obtained by Coculture of Monocytes and Mesenchymal Stromal Cells (PRS CK STORM).

Intercellular communication between monocytes/macrophages and cells involved in tissue regeneration, such as mesenchymal stromal cells (MSCs) and primary tissue cells, is essential for tissue regeneration and recovery of homeostasis. Typically, in the final phase of the inflammation-resolving process, this intercellular communication drives an anti-inflammatory immunomodulatory response. To obtain a safe and effective treatment to counteract the cytokine storm associated with a disproportionate immune response to severe infections, including that associated with COVID-19, by means of naturally balanced immunomodulation, our group has standardized the production under GMP-like conditions of a secretome by coculture of macrophages and MSCs. To characterize this proteome, we determined the expression of molecules related to cellular immune response and tissue regeneration, as well as its possible toxicity and anti-inflammatory potency. The results show a specific molecular pattern of interaction between the two cell types studied, with an anti-inflammatory and regenerative profile. In addition, the secretome is not toxic by itself on human PBMC or on THP-1 monocytes and prevents lipopolysaccharide (LPS)-induced growth effects on those cell types. Finally, PRS CK STORM prevents LPS-induced TNF-A and IL-1Β secretion from PBMC and from THP-1 cells at the same level as hydrocortisone, demonstrating its anti-inflammatory potency.

Oxytocin in the medial preoptic area facilitates male sexual behavior in the rat.

Oxytocin (OT) is a versatile neuropeptide that is involved in a variety of mammalian behaviors, and its role in reproductive function and behavior has been well established. The majority of pharmacological studies of the effects of OT on male sexual behavior have focused on the paraventricular nucleus (PVN), ventral tegmental area (VTA), hippocampus, and amygdala. Less attention has been given to the medial preoptic area (MPOA), a major integrative site for male sexual behavior. The present study investigated the effects of intra-MPOA administration of OT and (d(CH2)51, Tyr(Me)2, Thr4, Orn8, Tyr-NH29)-vasotocin, an OT antagonist (OTA), on copulation in the male rat. The relationship between OT receptor (OTR) binding levels in the MPOA and sexual efficiency was also explored. Microinjection of OT into the MPOA facilitated copulation in sexually experienced male rats, whereas similar injections of an OTA inhibited certain aspects of copulation but had no significant effect on locomotor activity in an open field. Contrary to expectation, sexually efficient males had lower levels of OTR binding in the rostral MPOA compared to inefficient animals. The present data suggest that OT activity in the MPOA is not necessary for the expression of male sexual behavior but is sufficient to facilitate copulatory behaviors and improve sexual efficiency in sexually experienced male rats. These data also suggest that OTR activity in the MPOA stimulates anogenital investigation, facilitates the initiation of copulation, and plays a role in the sensitization effect of the first ejaculation on subsequent ejaculations.

APOE Gene Associated with Cholesterol-Related Traits in the Hispanic Population.

Genetic variants in the apolipoprotein E (APOE) gene are associated with lipid metabolism and lipid-related traits in the non-Hispanic population. There have been limited studies regarding the association between the APOE gene and hypercholesterolemia in the Hispanic population; therefore, our aim for this study is to examine the APOE gene's associations with cholesterol level and its related phenotypes. The APOE gene consists of three different alleles, ε2, ε3, and ε4, with ε4 being associated with dementia and cardiovascular diseases. A total of 1,382 subjects were collected from the Texas Alzheimer's Research and Care Consortium (TARCC, N = 1320) and the Initial Study of Longevity and Dementia from the Rio Grande Valley (ISLD-RGV, N = 62). Questionnaires on demographics, medical history, and blood/saliva samples were collected and APOE genotypes were performed. We observed allele frequencies of the APOE ε3 (96.7%), ε4 (22.6%) and ε2 (6.8%) alleles, respectively. Multivariable logistic regression revealed a significant association between the APOE ε4 allele and hypercholesteremia (p = 1.8 × 10-4) in our studied Hispanic population. We prove for the first time, that the APOE ε4 allele increases the risk for hypercholesterol in Hispanics. Further research is needed to confirm and supports our current findings.

Gambling in Spanish Adolescents: Prevalence and Association with Mental Health Indicators.

Concern about the development of behavioral addictions in adolescence, including gambling, has increased in recent years. Evidence shows that problem gambling can lead to personal, social, or health problems. However, even though gambling is an illegal activity, studies on this problem are quite limited in Spain. The main objective of this study was to analyze the prevalence of gambling in adolescents in Spain. Moreover, gambling behaviors were examined according to gender and age, and their possible relationship with several mental health indicators was analyzed. The results showed that 20.6% of the adolescents who participated in the study had gambled money in the past year. The highest gambling prevalence was found in boys and in adolescents from the age of 16 years old. Moreover, the results showed that gambling behavior was related to different mental health indicators.

Neuropsychiatric Symptoms Among Hispanics: Results of the Maracaibo Aging Study.

BACKGROUND: Neuropsychiatric symptoms play an important role in diagnosing and clinical follow-up of cognitive impairment and dementia. OBJECTIVE: We investigated the relationship between neuropsychiatric symptoms, cognitive impairment, and dementia in Hispanics. METHODS: We included 529 participants (age ≥40 years) from the Maracaibo Aging Study with standardized neuropsychiatric assessments, including the Neuropsychiatric Inventory (NPI). Based on the Clinical Dementia Rating and the Mini-Mental State Examination scores, participants' cognitive status was categorized into normal cognition, mild/moderate, and severe cognitive impairment. Diagnosis of dementia was established in a consensus conference. Statistical analyses included multivariable logistic regression models and area under the curve (AUC). RESULTS: The mean age of participants was 59.3 years, and 71.8%were women. The proportion of dementia was 6.8%. Disturbed sleep, anxiety, and depression were the most common neuropsychiatric symptoms in the study sample. In crude analyses, the proportions of hallucinations, aberrant motor behavior, agitation/aggression, apathy, delusions, irritability, eating disturbance, depression, and euphoria were differently distributed among cognitive status groups (p < 0.05). After accounting for confounders, aberrant motor behavior and agitation/aggression remained significantly associated with cognitive impairment and dementia (p < 0.05). The inclusion of the NPI domains significantly improved the AUC to discriminate severe cognitive impairment and dementia compared to a basic model that included sex, age, education, alcohol, obesity, serum glucose, total cholesterol, hypertension, and stroke. CONCLUSION: Neuropsychiatric symptoms are associated with severe cognitive impairment and dementia. The addition of NPI items to the global cognitive assessment might help early detection of dementia in primary care settings.

Unplanned Transfers From Intermediate Care Units to Intensive Care Units: A Cohort Study.

This study evaluated unplanned transfers from the intermediate care unit (IMCU) to the intensive care unit (ICU) among urgent admissions. This retrospective, observational study was conducted in 2 ICUs and 1 IMCU. Three patterns of urgent admission were assessed: admissions to the ICU only, admissions to the IMCU only, and admissions to the IMCU with subsequent transfer to the ICU. Of 5296 admissions analyzed, 1396 patients (26.4%) were initially admitted to the IMCU. Of these, 172 (12.3%) were transferred from the IMCU to the ICU. Mortality was higher in patients transferred from the IMCU to the ICU than in the 3900 ICU-only patients (odds ratio, 3.22; 95% CI, 1.52-6.80). Most transfers from the IMCU to the ICU (135; 78.5%) were due to deterioration of the condition for which the patient was admitted. Patient transfers from the IMCU to the ICU were common, were associated with increased hospital mortality, and were mostly due to deterioration in the condition that was the reason for admission.

Hospital Pharmacist experience in the Intensive Care Unit: Plan COVID.

The Intensive Care Unit (ICU) of the University Hospital of Fuenlabrada was  forced to critically increase its capacity in the COVID-19 pandemic. The objective of this work is to describe the activities promoted by the pharmacist in the care  of the critically ill patient in this context. A new organizational structure was  designed, analyzing the tasks necessary to make the processes profitable. Two  pharmacists joined the critical patient care to help the pharmacist who was  already integrated in the ICU team. The development of the operational  structure was carried out on three levels. The healthcare activity highlights the  daily participation of pharmacists in the two clinical sessions in which the ICU  teams evaluated all cases and made decisions. This in turn facilitated the  pharmaceutical validation that was carried out in the critical units themselves. In addition, one of the pharmacists created the Immuno-COVID Committee, in  which they participated together with different specialists for therapeutic  decision-making in the most complex cases. On the other hand, the availability  of human and material resources allowed the implantation of centralized  elaboration in the Pharmacy Service of many intravenous mixtures, including  antibiotics elastomers Pumps for continuous infusion, and non-sterile  elaborations. In logistics management, in addition to the acquisition of COVID- 19 therapies, the reconciliation with nursing activity stands out. The physical presence of the pharmacist favored the detection of needs, the  availability in time of medications in the unit, including sterile and non-sterile  preparations, and coordination with the central pharmacy. In knowledge  management, the participation of the pharmacist in the working group for the  development of the hospital management protocol COVID-19 stands out. The  daily presence in the unit and the joint work with the entire multidisciplinary team demonstrate the value that the pharmacist can bring. In addition to  efficient resource management, support for clinical decision-making and  improvement actions, it provides the climate of inter-professional trust necessary to respond to the complexity of the critical patient and promote joint  projects.

La Unidad de Cuidados Intensivos del Hospital Universitario de Fuenlabrada se  vio obligada a aumentar de manera crítica su capacidad en la pandemia por  COVID-19. El objetivo de este trabajo es describir las actividades impulsadas por el farmacéutico en la atención del paciente crítico en este contexto. Se diseñó  una estructura organizativa nueva, analizando las tareas necesarias para  rentabilizar los procesos. Dos farmacéuticos se incorporaron a la atención del  paciente crítico para ayudar al farmacéutico que ya estaba integrado en el  equipo de la Unidad de Cuidados Intensivos. El desarrollo de la estructura  operativa se llevó a cabo en tres niveles. En la actividad asistencial destaca la  participación diaria de los farmacéuticos en las dos sesiones clínicas en las que  los equipos de la Unidad de Cuidados Intensivos valoraban todos los casos y  tomaban las decisiones. Esto, a su vez, facilitaba la validación farmacéutica que  se realizaba en las propias unidades de críticos. Además, uno de los  farmacéuticos ideó el Comité Inmuno-COVID, en el que participaban junto a  diferentes especialistas para la toma de decisiones terapéuticas en los casos más complejos. Por otro lado, la disponibilidad de recursos humanos y materiales  permitió implantar la elaboración de forma centralizada en el Servicio de Farmacia de muchas mezclas intravenosas, incluyendo elastómeros de  antibioterapia en perfusión continua, y de elaboraciones no estériles. En la  gestión logística, además de la adquisición de las terapias COVID-19, destaca la  conciliación con la actividad de enfermería. La presencia física del farmacéutico  favorecía la detección de necesidades, la disponibilidad en tiempo de  medicamentos en la unidad, incluyendo las elaboraciones estériles y no estériles, y la coordinación con la Farmacia central. En la gestión del conocimiento destaca la participación del farmacéutico en el grupo de trabajo para desarrollo del  protocolo hospitalario de manejo de la COVID-19. La presencia diaria en la  unidad y el trabajo conjunto con todo el equipo multidisciplinar ponen de  manifiesto el valor que el farmacéutico puede aportar. Además de una gestión  eficiente de los recursos, soporte en la toma de decisiones clínicas y acciones de  mejora, proporciona el clima de confianza interprofesional necesario para dar  respuesta a la complejidad del paciente crítico y promover proyectos conjuntos.

Early and extremely early multi-label fault diagnosis in induction motors.

The detection of faulty machinery and its automated diagnosis is an industrial priority because efficient fault diagnosis implies efficient management of the maintenance times, reduction of energy consumption, reduction in overall costs and, most importantly, the availability of the machinery is ensured. Thus, this paper presents a new intelligent multi-fault diagnosis method based on multiple sensor information for assessing the occurrence of single, combined, and simultaneous faulty conditions in an induction motor. The contribution and novelty of the proposed method include the consideration of different physical magnitudes such as vibrations, stator currents, voltages, and rotational speed as a meaningful source of information of the machine condition. Moreover, for each available physical magnitude, the reduction of the original number of attributes through the Principal Component Analysis leads to retain a reduced number of significant features that allows achieving the final diagnosis outcome by a multi-label classification tree. The effectiveness of the method was validated by using a complete set of experimental data acquired from a laboratory electromechanical system, where a healthy and seven faulty scenarios were assessed. Also, the interpretation of the results do not require any prior expert knowledge and the robustness of this proposal allows its application in industrial applications, since it may deal with different operating conditions such as different loads and operating frequencies. Finally, the performance was evaluated using multi-label measures, which to the best of our knowledge, is an innovative development in the field condition monitoring and fault identification.

Nighttime Blood Pressure Interacts with APOE Genotype to Increase the Risk of Incident Dementia of the Alzheimer's Type in Hispanics.

BACKGROUND: Dementia of the Alzheimer's type (DAT) impacts Hispanics disproportionately, with almost a twofold elevated risk of developing DAT, as well as earlier onset of the disease, than in non-Hispanic Whites. However, the role of main risk factors for DAT, such as APOE-ɛ4 and blood pressure (BP) levels, remains uncertain among Hispanics. OBJECTIVE: To investigate the association of APOE-ɛ4 and BP levels, measures with 24-h ambulatory BP monitoring, with incidence of DAT in an elderly cohort of Hispanics. METHODS: 1,320 participants from the Maracaibo Aging Study, free of dementia at the baseline, and with ambulatory BP measurements and APOE genotype available were included. Adjusted Cox proportional models were performed to examine 1) the incidence of DAT and 2) the relationship between BP levels and DAT according to APOE genotypes. Models were adjusted by competing risk of death before the onset of DAT. Model performance was assessed by likelihood test. RESULTS: The average follow-up time was 5.3 years. DAT incidence was 5.8 per 1000 person-year. APOE-ɛ4 carriers had a higher risk of DAT. In unadjusted analyses, conventional, 24-h, and nighttime systolic BP levels were significantly higher in participants who developed DAT and of APOE-ɛ4 carriers (p < 0.05). After adjustment for competing risks, only higher nighttime systolic BP was associated with DAT incidence, but only among subjects carrying APOE-ɛ4. CONCLUSION: In this Hispanic population, both APOE-ɛ4 genotype and assessment of nocturnal systolic BP (rather than diurnal or office BP) were necessary to estimate DAT risk.

Influence of biological sex on social behavior, individual recogntion, and non-associative learning in the adult gray short-tailed opossum (Monodelphis domestica).

Social behavior is critical for relationship formation and is influenced by myriad environmental and individual factors. Basic and preclinical research typically relies on rodent models to identify the mechanisms that underlie behavior; however, it is important to use non-rodent models as well. A major objective of the present study was to test the hypothesis that biological sex and social experience modulate the expression of social behavior in the adult gray short-tailed opossum (Monodelphis domestica), a non-traditional model. We also investigated the non-associative learning abilities of these animals. Following a period of social isolation, animals of both sexes were paired with a non-familiar, same-sex partner for 10 min on three different occasions, with 24-hour inter-trial intervals. We are the first research group to find significant sex differences in submissive and nonsocial behaviors in Monodelphis. Females displayed significantly higher durations of nonsocial behavior that increased over trials. Males were more aggressive; their latencies to the first attack and submissive behavior decreased over trials whereas these latencies increased for females; males' duration of submissive behavior increased over trials whereas it decreased for females. A different group of subjects habituated in response to repeated presentations to neutral odors and dishabituated in response to novel odors. In addition, both males and females demonstrated the ability to form social memories in a standard individual (social) recognition test. Our results contribute to the characterization of this marsupial species, an important first step in developing it as a model of complex social behaviors.

A regression-tree multilayer-perceptron hybrid strategy for the prediction of ore crushing-plate lifetimes.

Highly tensile manganese steel is in great demand owing to its high tensile strength under shock loads. All workpieces are produced through casting, because it is highly difficult to machine. The probabilistic aspects of its casting, its variable composition, and the different casting techniques must all be considered for the optimisation of its mechanical properties. A hybrid strategy is therefore proposed which combines decision trees and artificial neural networks (ANNs) for accurate and reliable prediction models for ore crushing plate lifetimes. The strategic blend of these two high-accuracy prediction models is used to generate simple decision trees which can reveal the main dataset features, thereby facilitating decision-making. Following a complexity analysis of a dataset with 450 different plates, the best model consisted of 9 different multilayer perceptrons, the inputs of which were only the Fe and Mn plate compositions. The model recorded a low root mean square error (RMSE) of only 0.0614 h for the lifetime of the plate: a very accurate result considering their varied lifetimes of between 746 and 6902 h in the dataset. Finally, the use of these models under real industrial conditions is presented in a heat map, namely a 2D representation of the main manufacturing process inputs with a colour scale which shows the predicted output, i.e. the expected lifetime of the manufactured plates. Thus, the hybrid strategy extracts core training dataset information in high-accuracy prediction models. This novel strategy merges the different capabilities of two families of machine-learning algorithms. It provides a high-accuracy industrial tool for the prediction of the full lifetime of highly tensile manganese steel plates. The results yielded a precision prediction of (RMSE of 0.061 h) for the full lifetime of (light, medium, and heavy) crusher plates manufactured with the three (experimental, classic, and highly efficient (new)) casting methods.

Preoptic glutamate facilitates male sexual behavior.

The medial preoptic area (MPOA) is a critical regulatory site for the control of male sexual behavior. We first measured glutamate in 2 min microdialysate samples from the MPOA before, during, and after copulation by male rats. There was a slight [approximately 140% of baseline (BL)] rise in extracellular glutamate when the female was presented, a significant increase (approximately 170% of BL) during periods of mounting and intromitting, and a very large increase in samples collected during ejaculation (approximately 300% of BL). A precipitous fall in levels occurred in the first postejaculatory sample; the magnitude of this fall was highly correlated with the length of the postejaculatory interval of quiescence. In experiment 2, we reverse-dialyzed a mixture of glutamate uptake inhibitors into the MPOA before and during mating; control animals received artificial CSF. The mixture increased extracellular glutamate (approximately 280% of BL), increased the number of ejaculations in the 40 min test, decreased ejaculation latency, and decreased the postejaculatory latency to resume copulation. These data, together with other findings that glutamate in the MPOA can elicit genital reflexes in anesthetized rats and that glutamate receptor antagonists in the MPOA impair copulation, strongly suggest that MPOA glutamate is a major facilitator of copulation and that the postejaculatory fall in glutamate regulates the postejaculatory interval.