Effects of Intracerebral Aminophylline Dosing on Catalepsy and Gait in an Animal Model of Parkinson's Disease.

Parkinson's disease (PD) is a progressive disorder characterized by the apoptosis of dopaminergic neurons in the basal ganglia. This study explored the potential effects of aminophylline, a non-selective adenosine A1 and A2A receptor antagonist, on catalepsy and gait in a haloperidol-induced PD model. Sixty adult male Swiss mice were surgically implanted with guide cannulas that targeted the basal ganglia. After seven days, the mice received intraperitoneal injections of either haloperidol (experimental group, PD-induced model) or saline solution (control group, non-PD-induced model), followed by intracerebral infusions of aminophylline. The assessments included catalepsy testing on the bar and gait analysis using the Open Field Maze. A two-way repeated-measures analysis of variance (ANOVA), followed by Tukey's post hoc tests, was employed to evaluate the impact of groups (experimental × control), aminophylline (60 nM × 120 nM × saline/placebo), and interactions. Significance was set at 5%. The results revealed that the systemic administration of haloperidol in the experimental group increased catalepsy and dysfunction of gait that paralleled the observations in PD. Co-treatment with aminophylline at 60 nM and 120 nM reversed catalepsy in the experimental group but did not restore the normal gait pattern of the animals. In the non-PD induced group, which did not present any signs of catalepsy or motor dysfunctions, the intracerebral dose of aminophylline did not exert any interference on reaction time for catalepsy but increased walking distance in the Open Field Maze. Considering the results, this study highlights important adenosine interactions in the basal ganglia of animals with and without signs comparable to those of PD. These findings offer valuable insights into the neurobiology of PD and emphasize the importance of exploring novel therapeutic strategies to improve patient's catalepsy and gait.

Effect of Short Photoperiod on Behavior and Brain Plasticity in Mice Differing in Predisposition to Catalepsy: The Role of BDNF and Serotonin System.

Seasonal affective disorder is characterized by depression during fall/winter as a result of shorter daylight. Catalepsy is a syndrome of some grave mental diseases. Both the neurotransmitter serotonin (5-HT) and brain-derived neurotrophic factor (BDNF) are involved in the pathophysiological mechanisms underlying catalepsy and depressive disorders. The aim was to compare the response of behavior and brain plasticity to photoperiod alterations in catalepsy-resistant C57BL/6J and catalepsy-prone CBA/Lac male mice. Mice of both strains were exposed for six weeks to standard-day (14 h light/10 h darkness) or short-day (4 h light/20 h darkness) conditions. Short photoperiod increased depressive-like behavior in both strains. Only treated CBA/Lac mice demonstrated increased cataleptic immobility, decreased brain 5-HT level, and the expression of Tph2 gene encoding the key enzyme for 5-HT biosynthesis. Mice of both strains maintained under short-day conditions, compared to those under standard-day conditions, showed a region-specific decrease in the brain transcription of the Htr1a, Htr4, and Htr7 genes. After a short photoperiod exposure, the mRNA levels of the BDNF-related genes were reduced in CBA/Lac mice and were increased in the C57BL/6J mice. Thus, the predisposition to catalepsy considerably influences the photoperiodic changes in neuroplasticity, wherein both C57BL/6J and CBA/Lac mice can serve as a powerful tool for investigating the link between seasons and mood.

Sleep deprivation induces late deleterious effects in a pharmacological model of Parkinsonism.

Parkinson's disease is a degenerative, chronic and progressive disease, characterized by motor dysfunctions. Patients also exhibit non-motor symptoms, such as affective and sleep disorders. Sleep disorders can potentiate clinical and neuropathological features and lead to worse prognosis. The goal of this study was to evaluate the effects of sleep deprivation (SD) in mice submitted to a progressive pharmacological model of Parkinsonism (chronic administration with a low dose of reserpine). Male Swiss mice received 20 injections of reserpine (0.1 mg/kg) or vehicle, on alternate days. SD was applied before or during reserpine treatment and was performed by gentle handling for 6 h per day for 10 consecutive days. Animals were submitted to motor and non-motor behavioral assessments and neurochemical evaluations. Locomotion was increased by SD and decreased by reserpine treatment. SD during treatment delayed the onset of catalepsy, but SD prior to treatment potentiated reserpine-induced catalepsy. Thus, although SD induced an apparent beneficial effect on motor parameters, a delayed deleterious effect on alterations induced by reserpine was found. In the object recognition test, both SD and reserpine treatment produced cognitive deficits. In addition, the association between SD and reserpine induced anhedonic-like behavior. Finally, an increase in oxidative stress was found in hippocampus of mice subjected to SD, and tyrosine hydroxylase immunoreactivity was reduced in substantia nigra of reserpine-treated animals. Results point to a possible late effect of SD, aggravating the deficits in mice submitted to the reserpine progressive model of PD.

Structure-Based Design of Novel G-Protein-Coupled Receptor TAAR1 Agonists as Potential Antipsychotic Drug Candidates.

The existing available antipsychotics have failed to manage the cognitive impairment of schizophrenia and induced a number of seriously undesirable effects. Trace amine-associated receptor 1 (TAAR1) has emerged as an ideal target for the design of antischizophrenia drugs, with the ability to mediate multiple psychological functions by sensing endogenous amine-containing metabolites without the side effects of catalepsy. In this work, a series of novel TAAR1 agonists were designed based on the structural analysis of the TAAR1 activation pocket. Among them, 6e displayed a potent TAAR1-Gs/Gq dual-pathway activation property, being different from that of the clinical drug candidate SEP-363856 with only TAAR1-Gs pathway activation. In rodent models, 6e significantly alleviated MK-801-induced schizophrenia-like cognitive phenotypes without inducing catalepsy. Furthermore, 6e·HCl exhibited favorable pharmacokinetic (T1/2 = 2.31 h, F = 39%) and safety properties. All these demonstrated that 6e·HCl may be used as a novel drug candidate for schizophrenia treatment.

Efficacy of Hypnosis and Catalepsy Induction in Functional Neurological Disorders.

BACKGROUND: Patients with Functional Neurological Disorder (FND) experience complex patterns of motor and/or sensory symptoms. Treatment studies of psychological interventions are promising but limited. OBJECTIVES: The aim of the current pilot study is to investigate the effect of treatment consisting of a combination of hypnosis and catalepsy induction on FND symptom severity. METHODS: A within-subject waiting list-control design was used with 46 patients diagnosed with FND. The treatment consisted of 10 sessions. The primary outcome measure was FND symptom severity (The Psychogenic Movement Disorder Rating Scale; PMDRS). The secondary outcome measures were psychological distress and quality of life. RESULTS: The repeated measures (RM) ANOVA for the PMDRS as outcome measure revealed a significant effect for time with a large effect size (η2 = 0.679). Pairwise comparisons indicated that the effect of time in the treatment period was significant for the measure of FND symptom severity, whereas the waiting list period was not. The effect remained stable even at 8 weeks post treatment. As for the additional measurement, general psychological distress and quality of life, no statistically significant differences between individual time points were found. CONCLUSIONS: This pilot study showed that eight sessions of treatment consisting of a combination of hypnosis and catalepsy induction was effective in reducing FND symptom severity. Some explanations and limitations are provided in the paper as well as several avenues of future research.

Enhancement of Haloperidol-Induced Catalepsy by GPR143, an L-Dopa Receptor, in Striatal Cholinergic Interneurons.

Dopamine neurons play crucial roles in pleasure, reward, memory, learning, and fine motor skills and their dysfunction is associated with various neuropsychiatric diseases. Dopamine receptors are the main target of treatment for neurologic and psychiatric disorders. Antipsychotics that antagonize the dopamine D2 receptor (DRD2) are used to alleviate the symptoms of these disorders but may also sometimes cause disabling side effects such as parkinsonism (catalepsy in rodents). Here we show that GPR143, a G-protein-coupled receptor for L-3,4-dihydroxyphenylalanine (L-DOPA), expressed in striatal cholinergic interneurons enhances the DRD2-mediated side effects of haloperidol, an antipsychotic agent. Haloperidol-induced catalepsy was attenuated in male Gpr143 gene-deficient (Gpr143-/y ) mice compared with wild-type (Wt) mice. Reducing the endogenous release of L-DOPA and preventing interactions between GPR143 and DRD2 suppressed the haloperidol-induced catalepsy in Wt mice but not Gpr143-/y mice. The phenotypic defect in Gpr143-/y mice was mimicked in cholinergic interneuron-specific Gpr143-/y (Chat-cre;Gpr143flox/y ) mice. Administration of haloperidol increased the phosphorylation of ribosomal protein S6 at Ser240/244 in the dorsolateral striatum of Wt mice but not Chat-cre;Gpr143flox/y mice. In Chinese hamster ovary cells stably expressing DRD2, co-expression of GPR143 increased cell surface expression level of DRD2, and L-DOPA application further enhanced the DRD2 surface expression. Shorter pauses in cholinergic interneuron firing activity were observed after intrastriatal stimulation in striatal slice preparations from Chat-cre;Gpr143flox/y mice compared with those from Wt mice. Together, these findings provide evidence that GPR143 regulates DRD2 function in cholinergic interneurons and may be involved in parkinsonism induced by antipsychotic drugs.

Coumarin analogue 3-methyl-7H-furo[3,2-g]chromen-7-one as a possible antiparkinsonian agent / El análogo de cumarina 3-metil-7H-furo[3,2-g]cromen-7-ona, un posible agente antiparkinsoniano

Abstract Introduction: Parkinson's disease is the second most common neurodegenerative disease. Monoamine oxidase B inhibitors are used in the treatment of this disease concomitantly with levodopa or as monotherapy. Several substituted coumarins have shown activity as inhibitors of monoamine oxidase B. Objective: To evaluate the possible antiparkinsonian effects of the coumarin analogue FCS005 (3-methyl-7H-furo[3,2-g]chromen-7-one) in mouse models, as well as its inhibitory activity towards monoamine oxidases (MAO) and its antioxidant activity. Materials and methods: FCS005 was synthesized and the reversal of hypokinesia was evaluated in the reserpine and levodopa models. Moreover, in the haloperidol model, its anticataleptic effects were evaluated. Additionally, the monoamine oxidase inhibitory activity and antioxidant activity of FCS005 were evaluated using in vitro and ex vivo studies, respectively. Results: FCS005 (100 mg/kg) caused the reversal of hypokinesia in the reserpine and levodopa models. This furocoumarin also presented anti-cataleptic effects at the same dose. Besides, it showed selective inhibitory activity towards the MAO-B isoform and antioxidant activity. Conclusion: These results attribute interesting properties to the compound FCS005. It is important to continue research on this molecule considering that it could be a potential antiparkinsonian agent.

Resumen Introducción. El segundo trastorno neurodegenerativo más común es la enfermedad de Parkinson. Los inhibidores de la monoamino oxidasa B se emplean en el tratamiento de esta enfermedad en monoterapia o concomitantemente con levodopa. Varios compuestos cumarínicos han mostrado actividad como inhibidores de la monoamino oxidasa B. Objetivo. Evaluar los posibles efectos antiparkinsonianos del análogo de la cumarina FCS005 (3-methyl-7H-furo [3,2-g ] chromen-7-one) en modelos de ratones, la actividad inhibitoria frente a las monoamino oxidasas (MAO) y la actividad antioxidante. Materiales y métodos. Se sintetizó la furanocumarina FCS005 y, en los modelos de reserpina y levodopa, se evaluó si producía reversión de la hipocinesia; en el modelo de haloperidol se evaluaron sus efectos anticatalépticos. Además, se evaluó in vitro la actividad inhibidora de MAO y, ex vivo, la actividad antioxidante del compuesto FCS005. Resultados. El compuesto FCS005 en dosis de 100 mg/kg produjo la remisión de la hipocinesia en los modelos de reserpina y de levodopa. Esta furanocumarina presentó efectos anticatalépticos con la misma dosis. Además, mostró tener actividad inhibitoria selectiva sobre la MAO B, así como efectos antioxidantes. Conclusión. Los resultados evidenciaron propiedades interesantes del compuesto FCS005. Es importante continuar investigando esta molécula porque puede ser un potencial agente antiparkinsoniano.

Catatonia y delirium: síndromes que pueden confluir en el paciente neuropsiquiátrico / Catatonia and Delirium: Syndromes that may Converge in the Neuropsychiatrie Patient

Resumen Introducción: La catatonia y el delírium son 2 síndromes diferentes e independientes. La catatonia es un síndrome psicomotor asociado a una variedad de enfermedades de diferentes causas médicas y está caracterizado por ausencia de actividad, inducción de posturas pasivas contra gravedad, la oposición o ausencia de respuesta ante estímulos externos, flexibilidad cérea, estereotipias, manierismos y ecofenómenos, entre otros. El delirium se caracteriza por alteraciones de la conciencia y cognitivas, principalmente atención y orientación, habitualmente de aparición aguda, que tiende a fluctuar durante el día y con evidencia de que la alteración es una consecuencia fisiológica directa de una enfermedad, una intoxicación o la abstinencia de alguna sustancia. A pesar de las diferencias y que las clasificaciones excluyen la posibilidad de que estos síndromes puedan presentarse juntos, varios reportes de casos y estudios en grupos de pacientes han planteado que pueden darse las 2 condiciones conjuntamente. Material y métodos: En el presente estudio se detectó a 16 pacientes hospitalizados en quienes concomitaban ambos síndromes, identificados mediante la escala Delirium rating scale-R (DRS-98) y la escala de Bush y Francis de Catatonia (BFCRS). Resultados: Se siguió el desenlace durante la hospitalización y su condición clínica al egreso. Estos pacientes en su mayoría tenían diagnósticos neurológicos, tuvieron una hospitalización larga, requirieron tratamiento con antipsicóticos y benzodiacepinas y sufrieron frecuentes complicaciones. Conclusiones: Catatonia y delirium son síndromes que pueden presentarse al mismo tiempo, lo que lleva a que los pacientes tengan peor desenlace y mayor riesgo de complicaciones.

Abstract Introduction: Catatonia and delirium are two different and independent syndromes. Catatonia is a psychomotor syndrome associated with a variety of diseases of different medical causes and is characterised by lack of activity, induction of passive postures against gravity, opposition or absence of response to external stimuli, waxy flexibility, stereotypies, mannerisms and echophenomena. Delirium is characterised by consciousness and cognitive alterations, mainly attention and orientation and usually of acute onset, which tend to fluctuate during the day and with evidence that the alteration is a direct physiological consequence of a disease, intoxication or substance withdrawal. Despite the differences and the fact that the classifications exclude the possibility that these syndromes may manifest together, several case reports and studies in groups of patients have postulated that the two conditions can occur together. Material and methods: In this study we identified 16 hospitalised patients who experienced both syndromes at the same time as confirmed by the Delirium Rating Scale-Revised (DRS-98) and the Bush-Francis Catatonia Rating Scale (BFCRS). Results: Patient outcome was followed during hospitalisation and the patients' clinical condition upon discharge. These patients had mostly neurological diagnoses, long hospital stays, required treatment with antipsychotics and benzodiazepines and had frequent complications. Conclusions: Catatonia and delirium are syndromes that can present at the same time, resulting in worse patient outcome and an increased risk of complications.

Catalepsia fármaco-inducida en el ratón / Drug-induced catalepsy in mice

La catalepsia fármaco-inducida en roedores es un modelo experimental muy utilizado para evaluar extrapiramidalismo. No existe una estandarización de la técnica, y en ocasiones las metodologías utilizadas son complicadas en su ejecución y en la evaluación de los resultados. También se han señalado diversos factores que pudieran llevar a una pseudocatalepsia o respuesta falsa positiva. El objetivo de este trabajo fue desarrollar una técnica sencilla y fiable donde no se observara pseudocatalepsia y verificar la viabilidad de su aplicación. Se describe un procedimiento utilizando ratones en un dispositivo artesanal y se muestran los resultados obtenidos luego de modificar las variables posición del animal, tiempo para realizar la observación y número de observaciones en un mismo animal. Se empleó haloperidol como droga de referencia. Se concluyó que la técnica propuesta es de fácil aplicación y consistente en sus resultados, sin que se observara pseudocatalepsia en la muestra utilizada

Drug-induced catalepsy in rodents is an experimental model commonly used to study extrapyramidalism. The technique has not been standardized, and the methodologies used are difficult to conduct and do not always facilitate the evaluation of results. Reference has also been made to various factors which might lead to pseudocatalepsy or to a false positive response. The objective of this study was to develop a simple, reliable technique in which pseudocatalepsy would not be observed, and verify the viability of its application. A description is presented of a procedure using mice in a handmade device and the results obtained after modifying the variables posture of the animal, time to make the observation, and number of observations for a given animal. Haloperidol was used as reference drug. It was concluded that the technique proposed is of easy application and yields consistent results, without any evidence of pseudocatalepsy in the sample used

Os êxtases da irmã germana: diferentes interpretações em torno das doenças nervosas no Brasil / The ecstasies of sister germana: different interpretations of nervous diseases in Brazil / Les extases de la sœur germana: les différentes interprétations des maladies nerveuses au Brésil / Los éxtasis de sor germana: diferentes interpretaciones acerca de las enfermedades nerviosas en Brasil

Apresenta diferentes concepções em torno dos êxtases de uma beata (Irmã Germana) que viveu em Minas Gerais no século XIX, o parecer do médico Antônio Gonçalves Gomide, seguido do exame de dois cirurgiões e da narrativa do naturalista Auguste de Saint-Hilaire. O objetivo é situar historicamente os textos, investigando as orientações teóricas dos autores e o modo como analisaram os êxtases da beata. A publicação dos documentos pode contribuir para o estudo dos saberes médico-mentais em inícios do século XIX no Brasil.

The article presents two different views of the ecstasies of a nun (Sister Germana) who lived in Minas Gerais, Brazil, in the nineteenth century. The first perspective was the opinion of Dr. Antônio Gonçalves Gomide, together with an examination by two surgeons; the second was a narrative by the naturalist Auguste de Saint-Hilaire. The goal is to historically situate the texts, investigate the theoretical orientations of the authors and note how they analyzed the woman's moments of ecstasy. The publication of these texts contributed to the study of medical and mental knowledge in the early 19th century in Brazil.

Cet article présente les différents aspects de l'extase d'une religieuse (la SŒur Germana) qui a vécu dans l'État de Minas Gerais au XIXe siècle, l'avis de son médecin Antonio Gonçalves Gomide, suivi de l'examen de deux chirurgiens et le récit du naturaliste Auguste de Saint-Hilaire. Notre travail est de situer historiquement les textes, d'enquêter sur les orientations théoriques des auteurs et sur la façon dont ils ont analysé l'extase de la sainte. Cet article a comme but de contribuer à l'étude des connaissances médicales et mentales au Brésil au début du XIXe siècle.

Se presentan diferentes concepciones acerca de los éxtasis de una beata (Sor Germana) que vivió en Minas Gerais en el siglo XIX, la opinión del médico Antônio Gonçalves Gomide, seguido por el examen de dos cirujanos y la narrativa del naturalista Auguste de Saint-Hilaire. El objetivo es situar históricamente los textos, investigando las orientaciones teóricas de los autores y el modo como analizaron los éxtasis de la beata. La publicación de los documentos puede contribuir para el estudio de los saberes médico-mentales en los inicios del siglo XIX en Brasil.

Os êxtases da Irmã Germana: diferentes interpretações em torno das doenças nervosas no Brasil / The ecstasies of Sister Germana: different interpretations of nervous diseases in Brazil / Les extases de la Sœur Germana: les différentes interprétations des maladies nerveuses au Brésil / Los éxtasis de Sor Germana: diferentes interpretaciones acerca de las enfermedades nerviosas en Brasil

Apresenta diferentes concepções em torno dos êxtases de uma beata (Irmã Germana) que viveu em Minas Gerais no século XIX, o parecer do médico Antônio Gonçalves Gomide, seguido do exame de dois cirurgiões e da narrativa do naturalista Auguste de Saint-Hilaire. O objetivo é situar historicamente os textos, investigando as orientações teóricas dos autores e o modo como analisaram os êxtases da beata. A publicação dos documentos pode contribuir para o estudo dos saberes médico-mentais em inícios do século XIX no Brasil.(AU)

The article presents two different views of the ecstasies of a nun (Sister Germana) who lived in Minas Gerais, Brazil, in the nineteenth century. The first perspective was the opinion of Dr. Antônio Gonçalves Gomide, together with an examination by two surgeons; the second was a narrative by the naturalist Auguste de Saint-Hilaire. The goal is to historically situate the texts, investigate the theoretical orientations of the authors and note how they analyzed the woman's moments of ecstasy. The publication of these texts contributed to the study of medical and mental knowledge in the early 19th century in Brazil.(AU)

Cet article présente les différents aspects de l'extase d'une religieuse (la SŒur Germana) qui a vécu dans l'État de Minas Gerais au XIXe siècle, l'avis de son médecin Antonio Gonçalves Gomide, suivi de l'examen de deux chirurgiens et le récit du naturaliste Auguste de Saint-Hilaire. Notre travail est de situer historiquement les textes, d'enquêter sur les orientations théoriques des auteurs et sur la façon dont ils ont analysé l'extase de la sainte. Cet article a comme but de contribuer à l'étude des connaissances médicales et mentales au Brésil au début du XIXe siècle.(AU)

Se presentan diferentes concepciones acerca de los éxtasis de una beata (Sor Germana) que vivió en Minas Gerais en el siglo XIX, la opinión del médico Antônio Gonçalves Gomide, seguido por el examen de dos cirujanos y la narrativa del naturalista Auguste de Saint-Hilaire. El objetivo es situar históricamente los textos, investigando las orientaciones teóricas de los autores y el modo como analizaron los éxtasis de la beata. La publicación de los documentos puede contribuir para el estudio de los saberes médico-mentales en los inicios del siglo XIX en Brasil.(AU)

Antônio Gonçalves Gomide: uma semiologia das doenças nervosas no Brasil / Antônio Gonçalves Gomide: a semiotics of nervous illnesses in Brazil

Analisa o parecer médico de Antônio Gonçalves Gomide, publicado em 1814. Trata-se de análise crítica realizada pelo médico, a fim de compreender as manifestações de uma beata, Germana Maria da Purificação, que viveu em Minas Gerais, entre os séculos XVIII e XIX. No texto o médico se contrapõe a um exame realizado por dois cirurgiões que declararam o estado da beata como sobrenatural. A intenção é analisar o parecer situando a concepção da patologia da beata para destacar a importância do documento na compreensão da constituição dos saberes médicos no Brasil. Procura-se ressaltar o fato de o texto ter sido um dos primeiros publicados sobre a medicina mental, podendo ser considerado um dos escritos fundadores dessa medicina que se inaugurava no Brasil no século XIX.

Antônio Gonçalves Gomide: uma semiologia das doenças nervosas no Brasil / Antônio Gonçalves Gomide: a semiotics of nervous illnesses in Brazil

Analisa o parecer médico de Antônio Gonçalves Gomide, publicado em 1814. Trata-se de análise crítica realizada pelo médico, a fim de compreender as manifestações de uma beata, Germana Maria da Purificação, que viveu em Minas Gerais, entre os séculos XVIII e XIX. No texto o médico se contrapõe a um exame realizado por dois cirurgiões que declararam o estado da beata como sobrenatural. A intenção é analisar o parecer situando a concepção da patologia da beata para destacar a importância do documento na compreensão da constituição dos saberes médicos no Brasil. Procura-se ressaltar o fato de o texto ter sido um dos primeiros publicados sobre a medicina mental, podendo ser considerado um dos escritos fundadores dessa medicina que se inaugurava no Brasil no século XIX.(AU)

Catalepsia induzida pelo lactato e atividade muscular forçada em ratos privados de sono / Catalepsy induced by lactate administration and forced muscular activity in rats

O estudo comparativo das homologias comportamentais é útil para a compreensão de diferentes aspectos dos transtornos psiquiátricos. Nesta perspectiva, o presente estudo avaliou os efeitos da privação de sono REM sobre a catalepsia. Ratos privados de sono REM por 4 dias foram submetidos à administração i.p. de lactato 10mM/Kg e exercício muscular forçado, sendo, então a catalepsia avaliada. O grupo de animais privados de sono mostrou menor incidência (50 por cento) de animais com catalepsia e média do tempo total de catalepsia menor (11,92 ± 4,12 minutos) em relação aos controles (91,7 por cento e 26,67 ± 5,86 min respectivamente), com significâncias estatísticas no limite (p=0,05). Conclui-se que, em uma situação de perigo prolongado, a catalepsia é disparada em uma segunda instância, após o esgotamento do repertório de enfrentamentos normais da vigília, e que o sono só é compensado após o término da situação de risco

Comparative studies of behavioral homologies help understand several aspects of psychiatric disorders. The present study evaluated the effect of REM-sleep deprivation on the catalepsy induced by lactate administration plus forced muscular activity. Rats deprived of REM-sleep for 96 hs were injected i.p. with lactate solution 10mM/kg and submitted to 5 minutes of forced muscular activity. Catalepsy was then evaluated. The number of animals displaying catalepsy (50%) and mean total catalepsy time (11,92 ± 4,12 minutes) were lower in sleep deprived animals than in controls (91.7% and 26.67 ± 5.86 min respectively), results being statistically significant at the limit level (p=0,05). It is concluded that in long lasting dangerous situations, catalepsy may be triggered after normal wakefulness coping possibilities are exhausted, and sleep being manifested only when the risk situation is over.

Catalepsia induzida pelo lactato e atividade muscular forçada em ratos privados de sono / Catalepsy induced by lactate administration and forced muscular activity in rats

O estudo comparativo das homologias comportamentais é útil para a compreensão de diferentes aspectos dos transtornos psiquiátricos. Nesta perspectiva, o presente estudo avaliou os efeitos da privação de sono REM sobre a catalepsia. Ratos privados de sono REM por 4 dias foram submetidos à administração i.p. de lactato 10mM/Kg e exercício muscular forçado, sendo, então a catalepsia avaliada. O grupo de animais privados de sono mostrou menor incidência (50 por cento) de animais com catalepsia e média do tempo total de catalepsia menor (11,92 ± 4,12 minutos) em relação aos controles (91,7 por cento e 26,67 ± 5,86 min respectivamente), com significâncias estatísticas no limite (p=0,05). Conclui-se que, em uma situação de perigo prolongado, a catalepsia é disparada em uma segunda instância, após o esgotamento do repertório de enfrentamentos normais da vigília, e que o sono só é compensado após o término da situação de risco(AU)

Catalepsy induced by lactate administration and forced muscular activity in rats. Comparative studies of behavioral homologies help understand several aspects of psychiatric disorders. The present study evaluated the effect of REM-sleep deprivation on the catalepsy induced by lactate administration plus forced muscular activity. Rats deprived of REM-sleep for 96 hs were injected i.p. with lactate solution 10mM/kg and submitted to 5 minutes of forced muscular activity. Catalepsy was then evaluated. The number of animals displaying catalepsy (50 percent) and mean total catalepsy time (11,92 ± 4,12 minutes) were lower in sleep deprived animals than in controls (91.7 percent and 26.67 ± 5.86 min respectively), results being statistically significant at the limit level (p=0,05). It is concluded that in long lasting dangerous situations, catalepsy may be triggered after normal wakefulness coping possibilities are exhausted, and sleep being manifested only when the risk situation is over(AU)

Variación del tiempo de catalepsia inducida por haloperidol en ratones debido a la administración de c. paradisi / Time variation of catalepsy induced by haloperidol in mice due to administration of c. paradisi

El zumo de pomelo (ZP) (Citrus paradisi) contiene una serie de bioflavonoides (Naringenina, Bergamotina, Furanocumarinas) que afectan la biodisponibilidad de algunos fármacos por medio de la inhibición del sistema enzimático CYP3A (enterico y hepático) que reduce el metabolismo de los mismos aumentado sus niveles plasmáticos. Utilizamos al Itraconazol (IZ), inhibidor de los componentes del sistema CYP450 científicamente comprobado, para comparar dicha actividad. Para poner de manifiesto la inhibición del sistema de isoenzimas por estas sustancias; utilizamos al Haloperidol (Ha), neuroléptico metabolizado por el CYP450 hepático que induce catalepsia, cuadro motor de inmovilización completa; en el cual no hay parálisis, pero tampoco hay movimiento, y tanto el tronco como las extremidades adoptan las posturas que se les impongan. Materiales y métodos: 48 ratones de la raza swiss albinos machos, distribuidos en seis grupos: Administración aguda: Grupo 1: Ha (0,7 mg/kg) ip. con Suero Fisiológico vo; Grupo Nro 2: Ha (0,7 mg/kg) ip. con IZ (1mg/kg) vo, Grupo Nro 3: Ha (0,7 mg/kg) ip. Con ZP vo. Y administración crónica: Grupo Nro 1: Ha (0,7 mg/kg) ip. administración única en el día 7, y Suero Fisiológico vo, Grupo Nro 2: Ha (0,7 mg/kg) ip. Administración única en el día 7, e IZ (1mg/kg) vo., Grupo Nro 3: Ha (0,7 mg/kg) ip. administración única en el día 7, y ZP vo. durante 7 días consecutivos. Existen claras diferencias entre los promedios de los tiempos de catalepsia observados entre la administración aguda y crónica de IZ y ZP. Es probable que lo observado sea producto de que una única exposición al ZP e IZ no sean capaces de inhibir el CYP450 hepático, pero si el entérico. Conclusión: la presencia de flavonoides en el zumo de Citrus paradisi produce una prolongación del tiempo de catalepsia inducida por haloperidol en ratones albinos machos suizos por inhibición del sistema CYP 450 3A4 hepático e intestinal.

Acute effects of selective serotonin reuptake inhibitors on neuroleptic-induced catalepsy in mice

Depression found in Parkinson disease (PD) usually responds to selective serotonin reuptake inhibitors (SSRIs). Drugs that modify experimental neuroleptic catalepsy (NC) might affect extrapyramidal symptoms in PD. Therefore, the effects of SSRIs on NC were tested in mice, 26-36 g, separated by sex. Catalepsy was induced with haloperidol (H; 1 mg/kg, ip) and measured at 30-min intervals using a bar test. An SSRI (sertraline, ST; paroxetine, PX; fluoxetine) or vehicle (C) was injected ip 30 min before H. Dunnett's test was used for comparison of means. ST (1-5 mg/kg) or PX (1-5 mg/kg) attenuated NC, with a similar inhibition found in both sexes (5 mg/kg, 180 min: ST - males: 124 ± 10 vs 714 ± 15 s in C; females: 116 ± 10 vs 718 ± 6 s in C; PX - males: 106 ± 10 vs 714 ± 14 s in C; females: 102 ± 10 vs 715 ± 14 s in C). At 0.3 mg/kg, neither of these drugs affected NC. Fluoxetine (1-25 mg/kg) also inhibited catalepsy, although the effect was not dose-dependent; no differences were observed between males and females (5 mg/kg, 180 min: males, 185 ± 14 vs 712 ± 14 s in C; females, 169 ± 10 vs 710 ± 19 s in C). For these SSRIs, maximal inhibition of NC was obtained with 5 mg/kg, 180 min after H. These results are consistent with the hypothesis that serotonergic mechanisms modulate nigrostriatal transmission, and suggest that SSRIs are possibly safe in depressive PD patients.

Ginkgo biloba leaf extract (EGb 761) enhances catalepsy induced by haloperidol and L-nitroarginine in mice

Ginkgo biloba extract EGb 761 has been reported to have therapeutic effects which have been attributed to anti-oxidant and free radical-scavenging activities, including a direct action on nitric oxide production. L G-nitro-arginine (L-NOARG), a nitric oxide synthase inhibitor, and haloperidol, a drug that blocks dopamine receptors, are both known to induce catalepsy in rodents. Nitric oxide has been shown to influence dopaminergic transmission in the striatum. The purpose of the present study was to evaluate the effect of the extract obtained from leaves of Ginkgo biloba tree EGb 761 on catalepsy induced by haloperidol or by L-NOARG. Albino Swiss mice (35-45 g, N = 8-12) received by gavage a single or repeated oral dose (twice a day for 4 days) of EGb 761 followed by ip injection of haloperidol or L-NOARG. After the treatments, the animals were submitted to behavioral evaluation using the catalepsy test. Acute treatment with 80 mg/kg EGb did not modify the catalepsy induced by L-NOARG but, the dose of 40 mg/kg significantly enhanced haloperidol-induced catalepsy measured at the 10th min of the test. After repeated treatment with 80 mg/kg EGb 761, a significant increase in the cataleptic effect produced by both haloperidol and L-NOARG was observed. These data show that repeated EGb 761 administration increases the effects of drugs that modify motor behavior in mice. Since the catalepsy test has predictive value regarding extrapyramidal effects, the possibility of pharmacological interactions between haloperidol and Ginkgo biloba extracts should be further investigated in clinical studies.

Dopaminergic profile of new heterocyclic N-phenylpiperazine derivatives

Dopamine constitutes about 80 percent of the content of central catecholamines and has a crucial role in the etiology of several neuropsychiatric disorders, including Parkinson's disease, depression and schizophrenia. Several dopaminergic drugs are used to treat these pathologies, but many problems are attributed to these therapies. Within this context, the search for new more efficient dopaminergic agents with less adverse effects represents a vast research field. The aim of the present study was to report the structural design of two N-phenylpiperazine derivatives, compound 4: 1-[1-(4-chlorophenyl)-1H-4-pyrazolylmethyl]-4-phenylhexahydropyrazine and compound 5: 1-[1-(4-chlorophenyl)-1H-1,2,3-triazol-4-ylmethyl]-4-phenylhexahydropyrazine, planned to be dopamine ligands, and their dopaminergic action profile. The two compounds were assayed (dose range of 15-40 mg/kg) in three experimental models: 1) blockade of amphetamine (30 mg/kg, ip)-induced stereotypy in rats; 2) the catalepsy test in mice, and 3) apomorphine (1 mg/kg, ip)-induced hypothermia in mice. Both derivatives induced cataleptic behavior (40 mg/kg, ip) and a hypothermic response (30 mg/kg, ip) which was not prevented by haloperidol (0.5 mg/kg, ip). Compound 5 (30 mg/kg, ip) also presented a synergistic hypothermic effect with apomorphine (1 mg/kg, ip). Only compound 4 (30 mg/kg, ip) significantly blocked the amphetamine-induced stereotypy in rats. The N-phenylpiperazine derivatives 4 and 5 seem to have a peculiar profile of action on dopaminergic functions. On the basis of the results of catalepsy and amphetamine-induced stereotypy, the compounds demonstrated an inhibitory effect on dopaminergic behaviors. However, their hypothermic effect is compatible with the stimulation of dopaminergic function which seems not to be mediated by D2/D3 receptors