Citrus limon (L.) Burm f. Essential Oil Has Anxiolytic and Sedative Properties by Modulating GABAA-Receptors

Abstract The high prevalence of anxiety disorders associated with pharmacotherapy side effects have motivated the search for new pharmacological agents. Species from Citrus genus, such as Citrus limon (sicilian lemon), have been used in folk medicine as a potential therapy to minimize emotional disorders. In order to searching for new effective treatments with fewer side effects, the present study evaluated the anxiolytic mechanism of action and the hypnotic-sedative activity from the Citrus limon fruit's peels essential oil (CLEO). Adults male Swiss mice were submitted to barbiturate-induced sleep test; elevated plus-maze (EPM) and light-dark box (LDB) (evaluation of the mechanism of action); rotarod; and catalepsy tests. CLEO oral treatment decreased latency and increased the sleep total time; moreover it induced in animals an increased the number of entries and percentage of time spent into open arms of the EPM; an increased the number of transitions and the percentage of time into light compartment in the LDB; which were only antagonized by flumazenil pretreatment, with no injury at motor function. Thus, results suggest that CLEO treatment induced an anxiolytic behavior suggestively modulated by the benzodiazepine binding site of the GABAA receptor or by an increase of GABAergic neurotransmission, without cause impairment in the motor coordination.

Oral Administration of Incense Resin (Styrax benzoin) Extract Enhances Spatial Learning, Memory, and Dendrite Complexity of Mice

Abstract Hippocampus is a part of the brain that has a major role in spatial learning and memory which can be affected by herbal extracts. Incense resin (Styrax benzoin) has been used by local communities to improve intelligence. However, there is no scientific evidence of the functions of Styrax benzoin for regulating hippocampal function. The aim of this study was intended to analyze and investigate the effect of incense resin on learning, memory, and dendrite complexity of mice. Three months old male Deutch Democratic Yokohama (DDY) mice were injected orally with graded doses of 100, 150, and 200 mg/kg of incense resin aqueous extract daily for 30 days. Spatial learning and memory performance levels were tested with Y-maze alternation, novel object recognition, and Morris water maze. The branches and maximum dendritic span in the dentate gyrus were observed by the Golgi-Cox staining. Overall, our results showed that incense resin extract increased learning and memory ability, and the number of dendrite branching in the dentate gyrus.

Oxiracetam ameliorates cognitive deficits in vascular dementia rats by regulating the expression of neuronal apoptosis/autophagy-related genes associated with the activation of the Akt/mTOR signaling pathway

Oxiracetam (ORC) is a commonly used nootropic drug for improving cognition and memory impairments. The therapeutic effect and underlying mechanism of ORC in vascular dementia (VaD) treatment remain unknown. In this study, 3-month-old male Sprague-Dawley rats with permanent bilateral common carotid artery occlusion-induced VaD were treated orally with low (100 mg/kg) or high (200 mg/kg) dose ORC once a day for 4 weeks. The results of the Morris water maze test and Nissl staining showed that ORC treatment significantly alleviated learning and memory deficits and neuronal damage in rats with VaD. Mechanistically, the protein levels of a panel of genes associated with neuronal apoptosis (Bcl-2, Bax) and autophagy (microtubule-associated protein 1 chain 3, Beclin1, p62) were significantly altered by ORC treatment compared with VaD, suggesting a protective role of ORC against VaD-induced neuronal apoptosis and autophagy. Moreover, the Akt/mTOR pathway, which is known to be the upstream signaling governing apoptosis and autophagy, was found to be activated in ORC-treated rats, suggesting an involvement of Akt/mTOR activation in ORC-rendered protection in VaD rats. Taken together, this study demonstrated that ORC may alleviate learning and memory impairments and neuronal damage in VaD rats by altering the expression of apoptosis/autophagy-related genes and activation of the Akt/mTOR signaling pathway in neurons.

The elevated gradient of aversion: a new apparatus to study the rat behavior dimensions of anxiety, fear, and impulsivity

Few behavioral tests allow measuring several characteristics and most require training, complex analyses, and/or are time-consuming. We present an apparatus based on rat exploratory behavior. Composed of three different environments, it allows the assessment of more than one behavioral characteristic in a short 3-min session. Factorial analyses have defined three behavioral dimensions, which we named Exploration, Impulsivity, and Self-protection. Behaviors composing the Exploration factor were increased by chlordiazepoxide and apomorphine and decreased by pentylenetetrazole. Behaviors composing the Impulsivity factor were increased by chlordiazepoxide, apomorphine, and both acute and chronic imipramine treatments. Behaviors composing the Self-protection factor were decreased by apomorphine. We submitted Wistar rats to the open-field test, the elevated-plus maze, and to the apparatus we are proposing. Measures related to exploratory behavior in all three tests were correlated. Measures composing the factors Impulsivity and Self-protection did not correlate with any measures from the two standard tests. Also, compared with existing impulsivity tests, the one we proposed did not require previous learning, training, or sophisticated analysis. Exploration measures from our test are as easy to obtain as the ones from other standard tests. Thus, we have proposed an apparatus that measured three different behavioral characteristics, was simple and fast, did not require subjects to be submitted to previous learning or training, was sensitive to drug treatments, and did not require sophisticated data analyses.

Thymoquinone reverses learning and memory impairments and brain tissue oxidative damage in hypothyroid juvenile rats / Timoquinona protegeu contra deficiências de aprendizagem e memória e danos nos tecidos cerebrais em ratos hipotireoidais juvenis

ABSTRACT In this study, the effect of thymoquinone (TQ) on propylthiouracil (PTU)-induced memory impairment was investigated in juvenile rats. The rats were grouped into control, Hypo, Hypo-TQ5 and Hypo-TQ10. Propylthiouracil increased latency time in the Morris water maze test and decreased delay in entering the dark compartment in the passive avoidance test. Both 5 mg/kg and 10 mg/kg doses of TQ decreased latency time in the Morris water maze test and increased delay in entering the dark compartment in a passive avoidance test. The PTU also increased malondialdehyde and nitric oxide metabolites in the brain while reduced the thiol content and superoxide dismutase and catalase activities and serum T4 level. Both doses of TQ decreased malondialdehyde and nitric oxide metabolites in the brain while enhanced the thiol content and superoxide dismutase and catalase activities and serum T4 level. The results of the present study showed that TQ protected against PTU-induced memory impairments in rats.

RESUMO Neste estudo, foi investigado o efeito da timoquinona (TQ) contra deficiências de memória induzidas por propiltiouracilo (PTU) em ratos juvenis. Os ratos foram agrupados em grupos: controle, Hypo, Hypo-TQ5, e Hypo-TQ10. O PTU aumentou o tempo de latência no teste do labirinto aquático de Morris (MWM) e diminuiu o atraso para entrar no compartimento escuro no teste de evasão passiva (PA). Ambas as doses de TQ diminuíram o tempo de latência no teste de MWM e aumentaram o atraso para entrar no compartimento escuro no teste de PA. O PTU também aumentou os metabolitos de malondialdeído (MDA) e óxido nítrico (NO) no cérebro, enquanto reduziu o teor de tiol e as atividades de superóxido dismutasa (SOD) e catalasa (CAT) e o nível sérico de T4. Ambas as doses de TQ diminuíram os metabolitos de MDA e de NO no cérebro, aumentaram o conteúdo de tiol e as atividades de SOD e CAT e o nível de T4 no soro. Os resultados do presente estudo mostraram que a TQ protegeu contra deficiências de memória induzidas por PTU em ratos.

Chronic intermittent exposure to ayahuasca during aging does not affect memory in mice

The Quechua term ayahuasca refers to a beverage obtained from decoctions of the liana Banisteriopsis caapi with leaves of Psychotria viridis. The ritualistic use of ayahuasca is becoming a global phenomenon, with some individuals using this beverage throughout life, including in old age. Cognitive impairment is a common manifestation during aging. There are conflicting reports on the ability of some ayahuasca compounds to exert neuroprotective or neurotoxic effects that could improve or impair learning and memory. Animal models provide a relevant and accessible means of investigating the behavioral effects of ayahuasca without the environmental conditions associated with the ritualistic use of the beverage. In this study, we investigated the influence of chronic ayahuasca exposure throughout aging on the spatial reference and habituation memories of mice. Twenty-eight male c57bl/6 mice (6 months old) received ayahuasca or water (1.5 mL/kg, orally) twice a week for 12 months and were tested in the Morris water maze (MWM), open field and elevated plus maze (EPM) tasks before and after treatment. During aging, there was significant impairment in the evocation (but not acquisition) of spatial reference memory and in habituation to the open field. There was also a decrease in locomotor activity in the open field and EPM tests, whereas the anxiety parameters were unaltered. Ayahuasca treatment did not alter any of these parameters associated with aging. These findings indicate that chronic exposure to ayahuasca during aging did not affect memory in mice.

The effects of memantine on recovery, cognitive functions, and pain after propofol anesthesia / Efeitos da memantina sobre a recuperação, funções cognitivas e dor após a anestesia com propofol

Abstract Objectives: Postoperative cognitive dysfunction refers to the problems associated with thought and memory that are often experienced after major surgery. The aim of this study is to evaluate the effects of intraperitoneally administered memantine on recovery, cognitive functions, and pain after propofol anesthesia. Methods: The study was conducted in Gazi University Animal Research Laboratory, Ankara, Turkey in January 2012. Twenty-four adult female Wistar Albino rats weighing 170-270 g were educated for 300 s in the radial arm maze (RAM) over three days. Group P was administered 150 mg kg−1 of intraperitoneal (IP) propofol; Group M was given 1 mg kg−1 of IP memantine; and Group MP was given 1 mg kg−1 of IP memantine before being administered 150 mg kg−1 of IP propofol. The control group received only IP saline. RAM and hot plate values were obtained after recovery from the groups that received propofol anesthesia and 30 min after the administration of drugs in other two groups. Results: The duration of recovery for Group MP was significantly shorter than Group P (p < 0.001), and the number of entries and exits in the RAM by Group MP was significantly higher during the first hour when compared to Group P (p < 0.0001). Hot plate values, on the other hand, were found to be significantly increased in all groups when compared to the control values, aside from Group C (p < 0.0001). Conclusion: In this study, memantine provided shorter recovery times, better cognitive functions, and reduced postoperative pain. From this study, we find that memantine has beneficial effects on recovery, cognitive functions, and pain after propofol anesthesia.

Resumo Objetivos: A disfunção cognitiva no pós-operatório refere-se a problemas associados ao pensamento e à memória que são frequentemente manifestados após uma cirurgia de grande porte. O objetivo deste estudo foi avaliar os efeitos da memantina administrada por via intraperitoneal sobre a recuperação, as funções cognitivas e a dor após a anestesia com propofol. Métodos: O estudo foi feito no Laboratório de Pesquisa com Animais da Universidade de Gazi, Ankara, Turquia, em janeiro de 2012. Vinte e quatro ratos albinos do sexo feminino, adultos, da linhagem Wistar, com 170-270 g, foram treinados durante 300 segundos no labirinto radial de oito braços (LRB) durante três dias. O Grupo P recebeu 150 mg/kg−1 de propofol por via intraperitoneal (IP), o Grupo H recebeu 1 mg/kg−1 de memantina IP e o Grupo MP recebeu 1 mg/kg−1 de memantina IP antes da administração de 150 mg/kg−1 de propofol (IP). O grupo controle recebeu apenas solução salina IP. Os valores do LRB e da placa quente foram obtidos após a recuperação dos grupos que receberam propofol e 30 minutos após a administração dos fármacos nos outros dois grupos. Resultados: O tempo de recuperação do Grupo MP foi significativamente menor do que o do Grupo P (p < 0,001) e o número de entradas e saídas do LRB do Grupo MP foi significativamente maior durante a primeira hora, em comparação com o Grupo P (p < 0,0001). Os valores da placa quente, por outro lado, foram significativamente maiores em todos os grupos, em comparação com os valores do grupo controle, exceto pelo Grupo C (p < 0,0001). Conclusão: No presente estudo, memantina proporcionou tempos mais curtos de recuperação, funções cognitivas melhores e reduziu a dor no pós-operatório. A partir deste estudo, descobrimos que a memantina tem efeitos benéficos sobre a recuperação, as funções cognitivas e a dor após anestesia com propofol.

Relative luminosity in the plus maze upon the exploratory behaviour of female Wistar rats / Efeito da luminosidade relativa em labirinto em cruz sobre o comportamento exploratório de fêmeas Wistar

Objective This study evaluated the provision of two configuration of the Elevated Pluz-Maze (EPM) by analizing the exploratory behaviour of female Wistar rats in different phases of the estrous cycle in EPMs with different gradients of luminosity between the open and enclosed arms (O/E∆Lux).Methods Female Wistar rats were treated with Midazolam (MDZ, 1.0 mg.kg-1) and were tested for their exploratory behaviour in either the EPM 10 O/E∆Lux or EPM 96 O/E∆Lux.Results A multiple regression analysis indicated that the O/E∆Lux is negatively associated with the %Open arm entries and %Open arm time, suggesting that as O/E∆Lux increases, the open arm exploration decreases. The estrous cycle phase did not influence the open-arm exploration in either EPM. MDZ- induced anxiolysis was detected in 96 O/E∆Lux EPM in all phases of the EC.Discussion Results of this study suggest the importance of the O/E∆Lux to establish the arm preference in the EPM, and to preserve the predictive validity of the EPM.

Objetivo Avaliar a provisão de duas configuracōes do Labirinto Elevado em Cruz (LEC) através do comportamento exploratório de ratas Wistar em diferentes fases do ciclo estral (CE) em LEC com diferentes gradientes de luminosidade entre os braços aberto e fechado (A/F∆Lux).Método Ratas Wistar foram tratadas com Midazolam (MDZ, 1.0 mg.kg-1) e foram testadas no LEC 10 A/F∆Lux ou LEC 96 A/F∆Lux.Resultados A análise de regressão múltipla indicou que o A/F∆Lux está negativamente associado com a % de entrada no braço aberto e % de tempo no braço aberto, sugerindo que no aumento do A/F∆Lux, a exploração do braço aberto diminui. A fase do CE não influenciou a exploração do braço aberto no LEC. A ansiólise induzida pelo MDZ foi demonstrada no 96 LEC A/F∆Lux em todas as fases do CE.Discussão Estes resultados sugerem a importância do A/F∆Lux para estabelecer a preferência da exploração do LEC e preservar a validade do LEC.

Puerarin protects against damage to spatial learning and memory ability in mice with chronic alcohol poisoning

We evaluated the effect of puerarin on spatial learning and memory ability of mice with chronic alcohol poisoning. A total of 30 male C57BL/6 mice were randomly divided into model, puerarin, and control groups (n=10 each). The model group received 60% (v/v) ethanol by intragastric administration followed by intraperitoneal injection of normal saline 30 min later. The puerarin group received intragastric 60% ethanol followed by intraperitoneal puerarin 30 min later, and the control group received intragastric saline followed by intraperitoneal saline. Six weeks after treatment, the Morris water maze and Tru Scan behavioral tests and immunofluorescence staining of cerebral cortex and hippocampal neurons (by Neu-N) and microglia (by Ib1) were conducted. Glutamic acid (Glu) and gamma amino butyric acid (GABA) in the cortex and hippocampus were assayed by high-performance liquid chromatography (HPLC), and tumor necrosis factor (TNF)-α and interleukin (IL)-1β were determined by ELISA. Compared with mice in the control group, escape latency and distance were prolonged, and spontaneous movement distance was shortened (P<0.05) by puerarin. The number of microglia was increased in both the cortex and hippocampal dentate gyrus (P<0.01), and neurons were reduced only in the hippocampal dentate gyrus (P<0.01) in puerarin-treated mice. In the model group, Glu and GABA levels decreased (P<0.05), and Glu/GABA, TNF-α, and IL-1β increased (P<0.01) with puerarin treatment, returning to near normal levels. In conclusion, puerarin protected against the effects of chronic alcohol poisoning on spatial learning and memory ability primarily because of anti-inflammatory activity and regulation of the balance of Glu and GABA.

Insulin-like growth factor (IgF)-I, IgF binding protein-3, and prostate cancer: correlation with gleason score

Introduction Non-androgenic growth factors are involved in the growth regulation of prostate cancer (PCa). Objective This is the first Brazilian study to correlate, in a population of patients operated for PCa, PSA, total testosterone, insulin-like growth factor-I (IGF-I) and insulin-like growth factor-binding protein-3 (IGFBP-3) with Gleason score and to compare with a control group with benign prostate hyperplasia (BPH). Materials and Methods This retrospective single-center study included 49 men with previously diagnosed PCa and 45 with previously diagnosed BPH. PSA, testosterone, IGF-I, IGFBP-3 were determined in both groups. Results PSA and IGFBP-3 levels were significantly higher in the PCa group as compared to the BPH group (p<0.001 and p=0.004, respectively). There was a significant difference when we compared the PSA before surgery (p<0.001) and at the inclusion in the study (p<0.001) and IGFBP3 (0.016) among patients with Gleason <7, ≥7 and BPH. In the PCa group, PSA, testosterone, IGF-I and IGFBP-3 levels were comparable between Gleason <7 and ≥7. Conclusions Our data suggest that in localized PCa, the quantification of PSA and, not of IGF-1, may provide independent significant information in the aggressiveness. IGFBP-3 could be a biochemical marker of disease control in PCa patients. .

Possible roles of COX-1 in learning and memory impairment induced by traumatic brain injury in mice

People who suffer from traumatic brain injury (TBI) often experience cognitive deficits in spatial reference and working memory. The possible roles of cyclooxygenase-1 (COX-1) in learning and memory impairment in mice with TBI are far from well known. Adult mice subjected to TBI were treated with the COX-1 selective inhibitor SC560. Performance in the open field and on the beam walk was then used to assess motor and behavioral function 1, 3, 7, 14, and 21 days following injury. Acquisition of spatial learning and memory retention was assessed using the Morris water maze on day 15 post-TBI. The expressions of COX-1, prostaglandin E2 (PGE2), interleukin (IL)-6, brain-derived neurotrophic factor (BDNF), platelet-derived growth factor BB (PDGF-BB), synapsin-I, and synaptophysin were detected in TBI mice. Administration of SC560 improved performance of beam walk tasks as well as spatial learning and memory after TBI. SC560 also reduced expressions of inflammatory markers IL-6 and PGE2, and reversed the expressions of COX-1, BDNF, PDGF-BB, synapsin-I, and synaptophysin in TBI mice. The present findings demonstrated that COX-1 might play an important role in cognitive deficits after TBI and that selective COX-1 inhibition should be further investigated as a potential therapeutic approach for TBI.

Learning and memory promoting effects of crude garlic extract.

Chronic administration of aged garlic extract has been shown to prevent memory impairment in mice. Acute and chronic (21 days) effects of marketed formulation of crude garlic extract (Lasuna) were evaluated on learning and memory in mice using step down latency (SDL) by passive avoidance response and transfer latency (TL) using elevated plus maze. Scopolamine (0.4 mg/kg, ip) was used to induce amnesia in mice and piracetam (200 mg/kg, ip) served as positive control. In the acute study, Lasuna (65 mg/kg, po) partially reversed the scopolamine-induced amnesia but failed to improve learning and memory in untreated animals. Chronic administration of Lasuna (40 mg/kg/day for 21 days) significantly improved learning both in control and scopolamine induced amnesic animals. Influence of Lasuna on central cholinergic activity and its antioxidant properties were also studied by estimating the cortical acetylcholinesterase (AchE) activity and reduced glutathione (GSH) levels respectively. Chronic administration of Lasuna inhibited AchE, while increasing GSH levels. Thus the results indicate that long-term administration of crude garlic extract may improve learning and memory in mice while the underlying mechanism of action may be attributed to the anti-AchE activity and anti-oxidant property of garlic.

Neurobiological effect of 7-nitroindazole, a neuronal nitric oxide synthase inhibitor, in experimental paradigm of Alzheimer’s disease.

Nitric oxide plays a role in a series of neurobiological functions, underlying behaviour and memory. The functional role of nNOS derived nitric oxide in cognitive functions is elusive. The present study was designed to investigate the effect of specific neuronal nitric oxide synthase inhibitor, 7-nitroindazole, against intracerebroventricular streptozotocin-induced cognitive impairment in rats. Learning and memory behaviour was assessed using Morris water maze and elevated plus maze. 7-nitroindazole (25 mg/kg, ip) was administered as prophylactically (30 min before intracerebroventricular streptozotocin injection on day 1) and therapeutically (30 min before the assessment of memory by Morris water maze on day 15). Intracerebroventricular streptozotocin produced significant cognitive deficits coupled with alterations in biochemical indices.These behavioural and biochemical changes were significantly prevented by prophylactic treatment of 7-nitroindazole. However, therapeutic intervention of 7-nitroindazole did not show any significant reversal. The results suggests that 7-nitroindazole can be effective in the protection of dementiainduced by intracerebroventricular streptozotocin only when given prophylactically but not therapeutically.

Brain tissue oxidative damage as a possible mechanism for the deleterious effect of a chronic high dose of estradiol on learning and memory in ovariectomized rats / Dano oxidativo ao tecido cerebral como possível mecanismo de efeito deletério da alta dose crônica de estradiol no aprendizado e memória de ratas ooforectomizadas

In addition to antioxidative effects, estrogens also exert pro-oxidative actions. The effect of chronic administration of a high dose of estradiol valerate on Morris water maze tasks and brain tissues oxidative damage was investigated. The Sham-Est and OVX-Est groups were treated with estradiol valerate (4 mg/kg) for 12 weeks. Escape latency and traveled path in the Sham-Est and OVX-Est groups were significantly higher than in the Sham and OVX groups (p≪0.01 and p≪0.001). In the probe trial, the animals of the Sham-Est and OVX-Est groups spent lower time in Q1 compared to Sham and OVX groups (p≪0.05 and p≪0.001). In Sham-Est and OVX-Est groups, the brain tissue total thiol concentration was significantly lower, and malondialdehyde (MDA) concentrations were higher than in the Sham and OVX groups (p≪0.05 and p≪0.001). It is concluded that administration of high exogenous levels of estradiol impairs performance and enhances oxidative stress.

Além dos efeitos antioxidantes, os estrógenos também têm ação pró-oxidativa. Foi investigado o efeito da administração crônica de alta dose de valereato de estradiol no desempenho do labirinto aquático de Morris e o dano oxidativo ao tecido cerebral. Os grupos Sham-Est e OVX-Est foram tratados com valereato de estradiol (4 mg/kg) por 12 semanas. O tempo de latência para escapada e o caminho percorrido foram significativamente maiores nos grupos Sham-Est e OVX-Est em relação aos grupos Sham e OVX (p≪0,01 e p≪0,001). No estudo probe, os animais dos grupos Sham-Est e OVX-Est levaram menos tempo no Q1 em comparação aos grupos Sham e OVX (p≪0,05 e p≪0,001). Nos grupos Sham-Est e OVX-Est, a concentração total de tiol foi significativamente menor, enquanto a concentração de malondialdehydo (MDA) for maior do que aquela dos grupos Sham e OVX (p≪0,05 e p≪0,001). Concluiu-se que a administração de altas doses de estradiol exógeno compromete o desempenho e aumenta o estresse oxidativo naqueles animais.

Intrahippocampal injection of 3 alpha diol [a testosterone metabolite] and indomethacin [3 alpha -HSD blocker], impair acquisition of spatial learning and memory in adult male rats

Hippocampus is essentially involved in learning and memory processes, and is known to be a target for androgen actions. The high density of the androgen receptors in hippocampus shows that there must be some relationship between androgens and memory. Androgen effects on spatial memory are complex and contradictory. Some evidence suggests a positive correlation between androgens and spatial memory. While some other reports indicated an impairment effect. The present study was conducted to assess the effect of 3 alpha diol on spatial discrimination of rats. Adult male rats were bilaterally cannulated into CA1 region of hippocampus and then received 3 alpha diol [0.2, 1, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [1.5, 3 and 6 micro g/ 0.5 micro L/side], indomethacin [3 micro g/ 0.5 micro L/side] + 3 alpha diol [1 micro g/ 0.5 micro L/side], 25-35 min before training in Morris Water Maze task. Our results showed that injection of 3 alpha diol [1, 3 and 6 micro g/ 0.5 micro L/side] and indomethacin [3 and 6 micro g/ 0.5 micro L/side] significantly increased the escape latency and traveled distance to find hidden platform. It is concluded that intra CA1 administration of 3 alpha diol and indomethacin could impair spatial learning and memory in acquisition stage. However, intra hippocampal injection of indomethacin plus 3 alpha diol could not change spatial learning and memory impairment effect of indomethacin or 3 alpha diol in Morris Water Maze task

Neurochemical and behavioral effects of green tea [Camellia sinensis]: a model study

Being rich in polyphenolic compounds such as flavonoids, green tea is suggested to be a potential candidate for the treatment of obesity, stress, depression, Parkinson's and other disorders. Since serotonin has an important role in the pathophysiology of these disorders, present study was designed to monitor the effects of green tea in rats. Green tea extract was provided to the male Albino Wistar rats for 5 weeks, and effects on behaviors were monitored. Results show a decrease in food intake after 5th week but not before. An increase in locomotive activities of the animals was observed, as monitored in novel as well as in familiar environment. Anxiolytic effects were observed in elevated plus maze but not in light dark activity box. An increase in dopamine and serotonin turnover was observed. Our results suggest that beneficial effects of green tea drinking might be due to alteration of serotonin and/or dopamine metabolism. We thereby propose that in further experiments, green tea should be administered in animal model of learned helplessness and effects on the development of adaptation to stress should be monitored. Neurochemical estimations of catecholamine and indoleamine in these animal models of stress exposed to green tea would help in understanding the anxiolytic effects of green tea

Dorsal periaqueductal gray stimulation facilitates anxiety-, but not panic-related, defensive responses in rats tested in the elevated T-maze

The escape response to electrical or chemical stimulation of the dorsal periaqueductal gray matter (DPAG) has been associated with panic attacks. In order to explore the validity of the DPAG stimulation model for the study of panic disorder, we determined if the aversive consequences of the electrical or chemical stimulation of this midbrain area can be detected subsequently in the elevated T-maze. This animal model, derived from the elevated plus-maze, permits the measurement in the same rat of a generalized anxiety- and a panic-related defensive response, i.e., inhibitory avoidance and escape, respectively. Facilitation of inhibitory avoidance, suggesting an anxiogenic effect, was detected in male Wistar rats (200-220 g) tested in the elevated T-maze 30 min after DPAG electrical stimulation (current generated by a sine-wave stimulator, frequency at 60 Hz) or after local microinjection of the GABA A receptor antagonist bicuculline (5 pmol). Previous electrical (5, 15, 30 min, or 24 h before testing) or chemical stimulation of this midbrain area did not affect escape performance in the elevated T-maze or locomotion in an open-field. No change in the two behavioral tasks measured by the elevated T-maze was observed after repetitive (3 trials) electrical stimulation of the DPAG. The results indicate that activation of the DPAG caused a short-lived, but selective, increase in defensive behaviors associated with generalized anxiety.

Decreased nitric oxide levels in the hippocampus may play a role in learning and memory deficits in ovariectomized rats treated by a high dose of estradiol / Níveis diminuídos de óxido nítrico no hipocampo podem ser importantes nos déficits de aprendizado e de memória em ratas ooforectomizadas tratadas com alta dose de estradiol

The effects of a high estradiol dose on memory and on nitric oxide metabolites in hippocampal tissues were investigated. Sham-Est and OVX-Est Groups were treated with 4 mg/kg of estradiol valerate for 12 weeks. Time latency and path length were significantly higher in the Sham-Est and OVX-Est Groups than in the Sham and OVX Groups, respectively (p<0.001). The animals in the Sham-Est and OVX-Est Groups spent lower time in the target quadrant (Q1) than those of the Sham and OVX Groups during the probe trial test (p<0.05 and <0.001, respectively). Significantly lower nitric oxide metabolite levels in the hippocampi of the Sham-Est and OVX-Est Groups were observed than in the Sham and OVX ones (p<0.001). These results suggest that decreased nitric oxide levels in the hippocampus may play a role in the learning and memory deficits observed after treatment with a high dose of estradiol, although the precise underlying mechanisms remain to be elucidated.

Os efeitos de uma alta dose de estradiol na memória e nos metabólitos do óxido nítrico de tecidos hipocampais foram estudados. Os Grupos Sham-Est e OVX-Est foram tratados com 4 mg/kg de valerato de estradiol por 12 semanas. O tempo de latência e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX, respectivamente (p<0,001). Os animais dos Grupos Sham-Est e OVX-Est passaram menos tempo na meta do quadrante (Q1) do que aqueles dos Grupos Sham e OVX durante o teste inicial (p<0,05 e <0,001, respectivamente). Níveis significativamente menores de metabólitos do óxido nítrico foram observados nos hipocampos dos Grupos Sham-Est e OVX-Est em relação aos Grupos Sham e OVX (p<0,001). Esses resultados sugerem que os níveis diminuídos de óxido nítrico no hipocampo podem ter um papel nos déficits de aprendizado e de memória, que são observados após tratamento com alta dose de estradiol, embora os mecanismos específicos envolvidos nestes achados ainda precisam ser elucidados.

Different effects of scopolamine on learning, memory, and nitric oxide metabolite levels in hippocampal tissues of ovariectomized and Sham-operated rats / Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico no tecido hipocampal de ratas ooforectomizadas e controles operadas sem ooforectomia

Different effects of scopolamine on learning, memory, and nitric oxide (NO) metabolites in hippocampal tissues of ovariectomized (OVX) and sham-operated rats were investigated. The animals in the Sham-Scopolamine (Sham-Sco) and OVX-Scopolamine (OVX-Sco) Groups were treated with 2 mg/kg scopolamine before undergoing the Morris water maze, while the animals in the Sham and OVX Groups received saline. The time latency and path length were significantly higher in both the Sham-Sco and the OVX-Sco Groups, in comparison with the Sham and OVX Groups, respectively (p<0.001). Significantly lower NO metabolite levels in the hippocampi of the Sham-Sco Group were observed, compared with the Sham Group (p<0.001), while there was no significant difference between the OVX-Sco and OVX Groups. The decreased NO level in the hippocampus may play a role in the learning and memory deficits induced by scopolamine. However, it seems that the effect of scopolamine on hippocampal NO differs between situations of presence and absence of ovarian hormones.

Diferentes efeitos da escopolamina no aprendizado, na memória e nos níveis dos metabólitos do óxido nítrico (ON) no tecido hipocampal de ratas ovariectomizadas (OVX) e controles com cirurgia sem ooforectomia (Grupo Sham) foram investigados. Os animais dos grupos Sham-Escopolamina (Sham-Sco) e OVX-Escopolamina (OVX-Sco) foram tratados com escopolamina 2 mg/kg antes de entrar no labirinto aquático de Morris, enquanto aqueles dos grupos Sham e OVX receberam solução salina. A latência de tempo e o comprimento do caminho foram significativamente maiores nos Grupos Sham-Sco e OVX-Sco em comparação com os grupos Sham e OVX, respectivamente (p<0,001). Foram observados níveis significativamente mais baixos de metabólitos do ON nos hipocampos do Grupo Sham-Sco em comparação aos níveis do Sham (p<0,001), enquanto não foi observada diferença significativa entre os Grupos OVX-Sco e OVX. A diminuição do nível de ON no hipocampo pode ter um papel no aprendizado e nos déficits de memória induzidos pela escopolamina. No entanto, parece que este efeito da escopolamina no ON hipocampal é diferente em situações de presença ou ausência de hormônios ovarianos.