Involvement of dopaminergic and cholinergic pathways in the induction of yawning and genital grooming by the aqueous extract of Saccharum officinarum L. (sugarcane) in rats.

Yawning, associated with genital grooming, is a physiological response that may be used for elucidating the mechanism of action of drugs. Preliminary analysis showed that aqueous extract (AE) of Saccharum induced yawns in rats. So, we aimed to quantify these behavioral responses and investigate the pharmacological mechanisms involved in these actions. During 120 min, after AE administration, the yawns and the genital grooming were quantified at 10 min intervals. Since dopaminergic and cholinergic pathways are implied in these responses, AE were evaluated in the presence of haloperidol 0.5 mg/kg and atropine 2 mg/kg. AE 0.5 g/kg increased the yawns, effect that was blocked both by haloperidol and atropine. Genital grooming could only be stimulated by AE 0.5 g/kg when dopaminergic receptors were blocked by haloperidol. However, it was inhibited when atropine was previously administered. So, we demonstrated a central action of Saccharum and it was postulated that neural circuits with the participation of dopaminergic and cholinergic pathways are involved. The fact that AE is comprised of innumerous compounds could justify the extract's distinct responses. Also, we cannot disregard the presence of different neural circuits that count on the participation of dopaminergic and cholinergic pathways and could be activated by the same induction agent.

Dual effects of hyperprolactinemia on carrageenan-induced inflammatory paw edema in rats.

OBJECTIVES: The effects of short-term 5-day and long-term 30-day hyperprolactinemia induced by domperidone (1.7 mg/kg/day, s.c.) or ectopic pituitary graft on the acute inflammatory response induced by carrageenan were evaluated in male rats. Both models of hyperprolactinemia effectively increased serum prolactin (PRL) levels. METHODS: The volume in milliliters of inflammatory edema was measured by plethysmography 1, 2, 3, 4, 6, 8 and 24 h after carrageenan injection. The areas under the inflammatory time-response curves were compared. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. RESULTS: In both domperidone-treated and pituitary graft-implanted animals, short-term 5-day hyperprolactinemia increased the inflammatory response, while long-term 30-day hyperprolactinemia had anti-inflammatory effects. Body weight was not affected by either short- or long-term hyperprolactinemia. CONCLUSION: These results show that PRL has biphasic effects on the carrageenan-induced inflammatory response.

Police officers under attack: resilience implications of an fMRI study.

OBJECTIVE: Crime is now a top-priority public-health issue in many urban areas. Sao Paulo's state police force was the target of gunfire attack on an unprecedented scale. Several officers were killed or wounded, and many more were affected by psychological trauma. We investigated the brain activity underlying trauma, the coping effect of psychotherapy, and resilience in a highly homogenous sample that experienced the same traumatic event. The design applied was a between-group comparison of cerebral blood-oxygenation-level-dependent signals and symptom scores of police officers with and without partial Posttraumatic Stress Disorder (pPTSD). METHOD: We used functional magnetic resonance imaging (fMRI) to investigate the retrieval of traumatic memories of 36 volunteers divided in three groups: (1) pPTSD policemen submitted to psychotherapy; (2) pPTSD policemen on the wait list; and (3) symptom-free (resilient) policemen. All participants were given a baseline fMRI scan and a follow-up scan some 40 days later. Not given psychotherapy, groups 2 and 3 were controls. RESULTS: Group 1 showed 37% fewer PTSD symptoms post-psychotherapy and their scores and neural expressions were comparable to Group 3 resilient policemen. A marked increased in medial prefrontal cortex (mPFC) activity was concomitant with decreased amygdala activity during traumatic memory retrieval in both resilient and pPTSD participants (after psychotherapy) and these findings were associated with symptom attenuation. CONCLUSIONS: Our results provide neurophysiological evidence of resilience in a high-risk group for PTSD. Psychotherapy may help to build narratives and resilient integrated translations of fragmented traumatic memories via mPFC, and thus weaken their sensory content while strengthening them cognitively.

Behavioral changes in Rattus norvegicus experimentally infected by Toxocara canis larvae.

Toxocara canis is a common canine nematode parasite and one of its possible transmission mechanisms is the predation of infected rodents by canids. Fifty Rattus norvegicus were used to study behavioral alterations in rodents infected by T. canis larvae. The rats were divided into three groups: G1, 20 rats infected with 300 T. canis eggs; G2, 20 rats infected with 2,000 T. canis eggs; and G3, 10 non-infected rats. Thirty and 60 days post-infection, rats from all the groups were submitted to an open-field apparatus for five min and subsequently, to an elevated plus-maze apparatus, again for five min. The data obtained indicated improvement in mobility (total locomotion time and rearing frequency) and exploratory behavior in infected rats, principally in G2, which provides some support for the hypothesis that behavioral alterations in rodents infected by Toxocara canis larvae enhance the transmission rate of this ascarid to dogs.

Behavioral changes in Rattus norvegicus experimentally infected by Toxocara canis larvae / Alterações de comportamento em Rattus norvegicus experimentalmente infectados por larvas de Toxocara canis

Toxocara canis is a common canine nematode parasite and one of its possible transmission mechanisms is the predation of infected rodents by canids. Fifty Rattus norvegicus were used to study behavioral alterations in rodents infected by T. canis larvae. The rats were divided into three groups: G1, 20 rats infected with 300 T. canis eggs; G2, 20 rats infected with 2,000 T. canis eggs; and G3, 10 non-infected rats. Thirty and 60 days post-infection, rats from all the groups were submitted to an open-field apparatus for five min and subsequently, to an elevated plus-maze apparatus, again for five min. The data obtained indicated improvement in mobility (total locomotion time and rearing frequency) and exploratory behavior in infected rats, principally in G2, which provides some support for the hypothesis that behavioral alterations in rodents infected by Toxocara canis larvae enhance the transmission rate of this ascarid to dogs.

Toxocara canis é um nematódeo parasita habitual do intestino delgado de cães. Um dos mecanismos conhecidos de transmissão para cães é representado pela predação de pequenos roedores que, como hospedeiros paratênicos albergam larvas de Toxocara canis em seus tecidos. Para avaliar a ocorrência de alterações de comportamento em roedores infectados por Toxocara canis 50 exemplares de Rattus norvegicus foram utilizados no experimento. Os animais foram divididos em três grupos: G1 - 20 ratos infectados com 300 ovos de Toxocara canis; G2 - 20 ratos infectados com 2.000 ovos de Toxocara canis e G3 - 10 ratos sem infecção. Trinta e 60 dias após a infecção avaliou-se a ocorrência de alterações comportamentais nos três grupos submetendo os animais, primeiramente, a uma arena de campo aberto durante cinco minutos e, a seguir, a labirinto em cruz elevado por mais cinco minutos. Os resultados obtidos indicaram aumento significativo da mobilidade (tempo total de movimentação e número de vezes em que os animais se levantaram nas patas traseiras) e comportamento exploratório nos ratos infectados, principalmente nos pertencentes ao G2, sugerindo a ocorrência de alterações comportamentais que favoreceriam a transmissão de Toxocara canis para canídeos por meio de relação presa-predador.

Muscular strength decrease in Rattus norvegicus experimentally infected by Toxocara canis.

The muscular strength of experimental infected Rattus norvegicus with 3rd. stage Toxocara canis larvae was investigated. Fifty Wistar rats, divided in three groups (G1-20 rats infected by 300 eggs of T. canis; G2-20 rats infected by 2,000 eggs of T. canis and G3-10 rats without infection) had been used. Ten and 30 days after infection the muscular strength in the fore-feet of the rats was checked; at the same time, the body weight was determined. No significative differences in the body weight were noted among the infected and control rats in both occasions. Otherwise, an impairment on the muscular strength was observed in rats infected with T. canis 30 days after inoculation.

Muscular strength decrease in Rattus norvegicus experimentally infected by Toxocara canis / Diminuição da força muscular em Rattus norvegicus experimentalmente infectados por Toxocara canis

The muscular strength of experimental infected Rattus norvegicus with 3rd. stage Toxocara canis larvae was investigated. Fifty Wistar rats, divided in three groups (G1 - 20 rats infected by 300 eggs of T. canis; G2 - 20 rats infected by 2,000 eggs of T. canis and G3 - 10 rats without infection) had been used. Ten and 30 days after infection the muscular strength in the fore-feet of the rats was checked; at the same time, the body weight was determined. No significative differences in the body weight were noted among the infected and control rats in both occasions. Otherwise, an impairment on the muscular strength was observed in rats infected with T. canis 30 days after inoculation.

Roedores são reconhecidos como hospedeiros paratênicos de Toxocara canis. Um dos mecanismos de transmissão desse ascarídeo para cães, seus hospedeiros habituais, consiste na predação de hospedeiros paratênicos, que albergam larvas de terceiro estágio em seus órgãos e tecidos, entre os quais músculos estriados. No presente trabalho estudou-se se a infecção por larvas de Toxocara canis provoca alterações na força muscular de exemplares de Rattus norvegicus experimentalmente infectados. Cinqüenta Rattus norvegicus foram divididos em três grupos: G1, com 20 ratos infectados com 300 ovos de Toxocara canis; G2, com 20 ratos infectados com 2.000 ovos do ascarídeo e G3, com 10 ratos sem infecção. Dez e 30 dias após a infecção determinou-se a força muscular nas patas dianteiras dos roedores; ao mesmo tempo, avaliou-se seu peso corporal. Não foram observadas diferenças no peso dos animais dos três grupos; contudo, verificou-se decréscimo na força muscular dos ratos infectados com 2.000 ovos após o 30º dia de infecção.

In vitro macrophage activity: biphasic effect of prolactin and indirect evidence of dopaminergic modulation.

OBJECTIVE: Prolactin (PRL), a peptide hormone produced by the pituitary gland, is involved in the interaction between the neuroendocrine and immune system. Since dopamine receptor antagonists increase serum levels of PRL, both PRL and dopamine receptors might be involved in the modulation of macrophage activity, providing means of communication between the nervous and immune systems. This study evaluated the effects of PRL and the dopamine antagonist domperidone (DOMP) on macrophage activity of female rats. METHODS: Oxidative burst and phagocytosis of peritoneal macrophages were evaluated by flow cytometry. Samples of peritoneal liquid from female rats were first incubated with PRL (10 and 100 nM) for different periods. The same procedure was repeated to evaluate the effects of DOMP (10 and 100 nM). RESULTS: In vitro incubation of macrophages with 10 nM DOMP decreased oxidative burst, after 30 min, whereas the PMA-induced burst was decreased by DOMP 10 nM after 2 and 4 h. Treatment with PRL (10 and 100 nM) for 30 min decreased oxidative burst and rate of phagocytosis (10 nM). After 2 h of incubation, 10 nM PRL decreased oxidative burst and phagocytosis intensity, but increased the rate of phagocytosis. On the other hand, after 4 h, PRL 10 and 100 nM increased oxidative burst and the rate of phagocytosis, but decreased intensity of phagocytosis. CONCLUSIONS: These observations suggest that macrophage functions are regulated by an endogenous dopaminergic tone. Our data also suggest that both PRL and dopamine exert their action by acting directly on the peritoneal macrophage.

Traumatic memories: bridging the gap between functional neuroimaging and psychotherapy.

OBJECTIVE: Neuroimaging studies have highlighted important issues related to structural and functional brain changes found in sufferers of psychological trauma that may influence their ability to synthesize, categorize, and integrate traumatic memories. METHODS: Literature review and critical analysis and synthesis. RESULTS: Traumatic memories are diagnostic symptoms of post-traumatic stress disorder (PTSD), and the dual representation theory posits separate memory systems subserving vivid re-experiencing (non-hippocampally dependent) versus declarative autobiographical memories of trauma (hippocampally dependent). But the psychopathological signs of trauma are not static over time, nor is the expression of traumatic memories. Multiple memory systems are activated simultaneously and in parallel on various occasions. Neural circuitry interaction is a crucial aspect in the development of a psychotherapeutic approach that may favour an integrative translation of the sensory fragments of the traumatic memory into a declarative memory system. CONCLUSION: The relationship between neuroimaging findings and psychological approaches is discussed for greater efficacy in the treatment of psychologically traumatized patients.

Cerebral blood flow changes during retrieval of traumatic memories before and after psychotherapy: a SPECT study.

BACKGROUND: Traumatic memory is a key symptom in psychological trauma victims and may remain vivid for several years. Psychotherapy has shown that neither the psychopathological signs of trauma nor the expression of traumatic memories are static over time. However, few studies have investigated the neural substrates of psychotherapy-related symptom changes. METHOD: We studied 16 subthreshold post-traumatic stress disorder (PTSD) subjects by using a script-driven symptom provocation paradigm adapted for single photon emission computed tomography (SPECT) that was read aloud during traumatic memory retrieval both before and after exposure-based and cognitive restructuring therapy. Their neural activity levels were compared with a control group comprising 11 waiting-list subthreshold PTSD patients, who were age- and profile-matched with the psychotherapy group. RESULTS: Significantly higher activity was observed in the parietal lobes, left hippocampus, thalamus and left prefrontal cortex during memory retrieval after psychotherapy. Positive correlations were found between activity changes in the left prefrontal cortex and left thalamus, and also between the left prefrontal cortex and left parietal lobe. CONCLUSIONS: Neural mechanisms involved in subthreshold PTSD may share neural similarities with those underlying the fragmented and non-verbal nature of traumatic memories in full PTSD. Moreover, psychotherapy may influence the development of a narrative pattern overlaying the declarative memory neural substrates.

Periaqueductal gray cholecystokinin infusions block morphine-induced disruption of maternal behavior.

Cholecystokinin (CCK) and opiates interaction is critical for maintaining maternal behavior during lactation. Morphine inhibits while CCK restores maternal behavior. Recently we have shown that periaqueductal gray (PAG) is a region critically involved in the opioidergic blockade of maternal behavior. A critical level of morphine-induced activation of the rostral lateral PAG is required to inhibit maternal behavior in lactating rats. Since central CCK injections reverted morphine-induced inhibition of maternal behavior, we tested whether this peptide would act similarly in the PAG. This hypothesis was confirmed in experiments showing that morphine's inhibitory effect on maternal responsiveness was blocked by 1.0 and 0.2 nmol CCK injections into the rostral PAG, but not in nearby regions of the mesencephalic reticular nucleus. To test for possible compensatory changes the CCK2 receptor due to morphine treatments the expression of CCK2 receptor mRNA was evaluated in the PAG. PAG CCK2 receptor cDNA amplification revealed no difference in morphine treated animals. These results broaden understanding of the role played by CCK in the PAG. This CCK action might not depend on changes in its receptor.

Rapidly induced dopaminergic supersensitivity: D1/D2 receptor participation and its prevention by an MAO-inhibitor.

The dopaminergic system requires combined dopamine D1/D2 receptor stimulation to express its activity; a phenomenon called synergism D1/D2. Dopamine receptors develop supersensitivity following dopamine de-afferentation and/or reserpine treatment. Acute supersensitivity occurs with reserpine treatment. The breakdown of D1/D2 synergism has been proposed implicating the genesis of this kind of supersensitivity. We sought to determine the best conditions for inducing acute dopaminergic supersensitivity evaluated by apomorphine-induced stereotyped behaviour, to examine whether D1/D2 synergism breakdown occurs in this reserpine-induced acute supersensitivity model, and whether it can be prevented by the monoamino-oxidase (MAO) inhibitor selegiline. Reserpine (2.0 mg/kg) was injected 3 h before apomorphine (0.6 mg/kg) induced stereotypy. D1/D2 synergism was investigated using specific antagonists (D1-SKF 83566 2.5 mg/kg, D2-haloperidol 2.0 mg/kg) and selegiline (10 mg/kg) was used to analyze the influence of dopamine "de-novo" synthesis. All antagonist treatments suppressed stereotypy and selegiline prevented supersensitivity. These data suggest that reserpine-induced acute dopaminergic supersensitivity is not due to the breakdown of D1/D2 synergism and such supersensitivity can be prevented by recently synthesised dopamine.

Promovendo resiliência em vítimas de trauma psicológico / Fostering resilience in psychological trauma victims

A exposição a eventos estressores e violentos ocorre com relativa freqüência em grande parte da população. A busca pela compreensão das respostas ao trauma está voltada também para a contribuição dos fatores da personalidade. A maneira como os indivíduos processam o evento estressor é crítica para a determinação ou não do trauma. O encéfalo não armazena propriamente registros factuais, mas traços de informações que serão usados para recriar memórias, as quais nem sempre expressam um retrato completamente fidedigno da experiência passada. Sempre que um evento traumático é recordado, este pode submeter-se a mudanças cognitivas e emocionais. Postulamos que os psicoterapeutas devem trabalhar, além do evento traumático em si, os diálogos internos que mantêm a relação patológica com o episódio passado. A exposição imaginária e a reestruturação cognitiva podem auxiliar as vítimas de experiências traumáticas a evoluir a partir de suas experiências negativas, com o desenvolvimento de diálogos internos saudáveis e resilientes.

The use of sudden darkness in mice: a behavioural and pharmacological approach.

Sudden darkness is a non-invasive behavioural analysis tool which increases motor activity and decreases anxiety in rats. It has been shown in previous studies that in rats, dark test conditions can also modify behavioural responses to drugs acting on the dopaminergic system. The increasing use of transgenic mice in behavioural research has raised interest in developing new tests for phenotyping mice. Hence, the aim of the present study was to adapt the sudden darkness paradigm for mice. In the first part of this study, effects of sudden darkness on the performance of mice in the elevated plus maze test were evaluated. Both genders of two mouse strains (Swiss and Balb/c) were tested either in high light intensity conditions or were exposed to sudden darkness. In the second part, responses to the 5-HT(1A) receptor agonist 8-OH-DPAT (0.5 and 1.0 mg/kg) and 5-HT(2C) receptor agonist mCPP (1.0 and 2.0 mg/kg) were investigated in male Swiss mice. Sudden darkness induced a clear anxiolytic effect in male and female Swiss mice. In Balb/c mice, anxiety-related behaviour was only decreased in females, whereas in males the anxiety state remained unchanged. An increase in motor activity was only observed in male Swiss mice; in the other groups, sudden darkness did not affect locomotion. Depending on the light conditions used, the behavioural response to receptor agonists was more evident: 8-OH-DPAT (1.0 mg/kg) only significantly decreased the anxiety state when mice were tested under high levels of illumination, whereas the anxiogenic effect of mCPP (1.0 and 2.0 mg/kg) was only evident in the dark. This study suggests that the sudden darkness paradigm is also a useful tool for the analysis of mice and can be used to modulate the anxiety level without administering drugs. Depending on the mouse strain tested, the same effects on anxiety and motor activity were observed as have been shown for rats.

A comparative study of the anticholinesterase activity of several antipsychotic agents.

Drug-induced inhibition of plasma and tissue cholinesterase activity was evaluated in rats. The dopamine receptor antagonists haloperidol (HALO), chlorpromazine (CPZ), thioridazine (THIO), fluphenazine (FLU), clozapine (CLO) and sulpiride (SULP), used as neuroleptics, were tested. Two biochemical parameters were measured in vitro: the minimal effective concentration (MEC) for cholinesterase inhibition and the 50% inhibitory concentration (IC50). In addition, animals were tested for rotational activity after a unilateral intrastriatal injection of the drugs. The doses used for each drug were previously determined IC50s. After unilateral striatal drug injection, rats were challenged with intraperitoneal amphetamine injection in order to stimulate rotation. All drugs tested induced decreases in cholinesterase activity. Plasma MEC for THIO, FLU, HALO and CPZ were significantly lower than for CLO and SULP. In striatum, the MEC for TIO, CPZ and FLU was significantly lower than for HAL. According to plasma IC50, THIO, CPZ and CLO are potent cholinesterase inhibitors. CLO showed the lowest potency of cholinesterase inhibition in the striatum and THIO showed the highest potency in plasma and striatum. In conclusion, anticholinesterase activity is not related to D(2) receptor blockade or antipsychotic potency; and therefore the antipsychotic effects are not related to an increase in acetylcholine. All drugs induced similar contralateral rotation, except for CLO that was different from SULP and was not different from its control. Since equivalent cholinesterase inhibitory concentrations were used for all drugs and no differences in nigrostriatal behavioral effects were observed, these data suggest the participation of an important cholinergic component in this behavior. Therapeutically, the stronger the cholinesterase inhibition is, the more potent the cholinergic effects are and, consequently, the induction of extrapyramidal symptoms becomes more feasible.

Modulation by sudden darkness of apomorphine-induced behavioral responses.

Sudden darkness increases motor activity and decreases anxiety. In the present study, we focused on the role of dopaminergic mechanisms involved in the effects of sudden darkness. The influence of sudden darkness on the behavioral effects of low (0.05 and 0.1 mg/kg) and high (0.25, 0.45 and 0.6 mg/kg) doses of apomorphine (APO) was tested. We assayed the effects of low APO doses on yawning-penile erection syndrome (YES; 0.05 and 0.1 mg/kg) and on motor activity (0.05 mg/kg), and the effects of high APO doses on motor activity (0.25 mg/kg) and stereotyped behavior (0.45 mg/kg and 0.6 mg/kg). Spontaneous total and genital grooming of male and female rats were also recorded. Sudden darkness modified some spontaneous behaviors and also modulated several APO-induced behavioral effects. It increased spontaneous total grooming and genital grooming in male rats but had no effect on these parameters in female rats. These results show sexual dimorphism for total and genital grooming in both control and sudden darkness conditions. APO was able to induce YES in a dose-dependent manner. Sudden darkness decreased yawning elicited by both 0.05 and 0.1 mg/kg of the drug. No other parameter of YES was modified. In the open-field test, sudden darkness increased total locomotion and rearing and decreased immobility duration. APO at a dose of 0.05 mg/kg had the opposite effect on these parameters under light conditions; none of them were modified by sudden darkness. Animals treated with APO at 0.25 mg/kg, a dose that augmented total locomotion and rearing and diminished immobility duration, were clearly divided into two groups according to their responses, i.e., hypo- and hyper-responsive rats. Sudden darkness improved total locomotion and rearing, reduced immobility duration and total grooming in the hyporesponsive group, and showed no effects on the hyper-responsive group. Sudden darkness caused no modifications of stereotyped behavior. These results may be due to a sudden darkness-induced physiological release of dopamine that diminishes pre-synaptic responses to APO and increases low-intensity post-synaptic responses such as motor activity without modifying high-intensity post-synaptic responses such as stereotyped behavior.

Puerperal blockade of cholecystokinin (CCK1) receptors disrupts maternal behavior in lactating rats.

Blockade of cholecystokinin (CCK) receptors potentiates the morphine-induced disruption of maternal behavior. The present study was undertaken to determine whether treatment with lorglumide, a CCK1 antagonist during late pregnancy and early lactation can influence the maternal behavior during lactation. A possible influence of this treatment on general activity was also assessed. Twenty-seven female Wistar rats were pretreated with lorglumide (1.0mg/kg/day; sc) or saline for seven days, starting on the 17th d of pregnancy. After the withdrawal of this treatment, animals were acutely challenged with saline on day 5 and with morphine sulfate (3.0mg/kg; sc) on days 6,10, and 17 of lactation. Groups were pretreated with saline and challenged with saline (group SS) and morphine (group SM), pretreated with lorglumide and challenged with saline (group LS) and morphine (group LM). Animals were also tested for general activity on days 25 and 33 postpartum after an acute challenge with saline and morphine, respectively. Maternal behavior testing began 30 min after the acute injections at which time pups were placed throughout each mother's cage. Latencies for pup retrieval, grouping, crouching and for full maternal behavior responses were scored. Lorglumide pretreatment inhibited maternal behavior of LS vs SS group and potentiated the morphine-induced disruption of this behavior in all days of test (LM vs SM group). No significant differences were found in general activity on days 25 and 33 postpartum. These data suggest that blockade of CCK1 receptors during puerperal period has long-term implications for maternal behavior.