Effect of leptin on spatial learning, memory and blood glucose level in streptozotocin induced diabetes mellitus in male wistar albino rats

Background: Diabetes mellitus is known to cause cognitive impairment that can be possibly attributed to deficient levels of leptin in diabetic animals. This study was undertaken to study the effect of administration of leptin on spatial learning, memory and blood glucose levels in diabetic rats.Methods: Rats were divided into three groups. The first group was the control group. Diabetes was induced in groups 2 and 3 by streptozotocin (STZ) injection (60 mg/kg) intraperitoneally. Group 2 received saline while group 3 received leptin (0.1 mg/kg) subcutaneously for 10 days from 4th day of STZ administration. Behavioural assessment was done in T maze after 21 days of the last injection of leptin. Blood glucose levels were also analysed.Results: The number of correct arm entries decreased while time spent being immobile and time spent to reach the correct arm increased in the diabetic group when compared to the control group and correct arm entries increased while time spent immobile and time spent to reach the correct arm decreased with leptin treatment when compared to the diabetic control rats. Blood glucose levels increased in the diabetic rats while leptin administration reduced blood glucose levels in the group 3.Conclusions: Our study suggests that leptin can improve learning and memory while also producing a slight reduction in the blood glucose levels in diabetic rats.

Effect of Plumeriarubra(Apocynaceae) leaf extracts, a repellent of rice-field rats (Rattusargentiventer), on its metabolism and daily activity

Introduction: Rice-field rats are one of the most important pests because it can give large losses in all planting seasons including the storehouse. Synthetic rodenticide is the most commonly used of chemical technique for controlling rice-field rats. The application of these materials indirectly causes negative impacts; one of them is for the environment. As an alternative for controlling rice-field rats, natural materials can be used as a repellent. Objective: To examine the effects of methanol extract of Plumeriarubra leaves on metabolism, daily activity patterns, and its potency as a repellent of the rice-field rat. Methods: The experiments were conducted at the Laboratory of Pests, UniversitasPadjadjaran involves choice test (T-maze arena), and the Laboratory of Rats, Indonesian Center for Rice Research involves no-choice test (metabolic cage) from February until May 2019. The observations including food (g), water consumption (ml), feces production (g), urine production (ml), body weight (g), and its changes (%), also the daily activities (time spent for locomotion, foraging, and resting).The treatment was done with three replications for twelve mature male and twelve mature non-pregnant females. Data experiments analysis followed by a T-test. Results: Rice-field rats on the T-Maze arena avoided consuming food and beverage that close to methanol extract of Plumeriarubra leaves treatment. The treatment of methanol extract of Plumeria leaves in metabolic cage caused metabolic disorder of rice-field rat, which was significantly indicated by the decrease of the average consumption of food by 2.28 g and excretion of feces by 0.34 g, and also the increase of average consumption of beverage by 3.89 ml, excretion of urine by 3.15 ml, and body weight by 6.67 g. The treatment also caused daily activity patterns disorder of rice-field rats, which was significantly indicated by the increase of the average percentage of time for movement activities (locomotion) by 7.64 % and the decrease of time for eating and drinking activities (foraging) by 16.46 %. Conclusion: Methanol extract of Plumeria leaves affects a repellent for the rice-field rat.

Introducción: Las ratas arroceras son una de las plagas más importantes porque pueden producir grandes pérdidas en todas las temporadas de siembra, incluso en el almacenaje. La técnica química más utilizada para controlar las ratas de los arrozales es el raticida sintético. Sin embargo, la aplicación de estos químicos provoca indirectamente impactos negativos, por ejemplo, en el ambiente. Una alternativa para controlar la rata arrocera es la utilización de compuestos naturales como repelentes. Objetivo: Examinar los efectos del extracto metanólico de hojas de Plumeria rubra sobre el metabolismo, los patrones de actividad diaria en las ratas arroceras y su potencial como repelente. Métodos: Los experimentos se llevaron a cabo en Laboratory of Pests, UniversitasPadjadjaran usando la prueba T-maze arena, y en Laboratory of Rats, Indonesian Center for Rice Research usando la prueba metaboliccage, desde febrero hasta mayo 2019. Las observaciones incluyeron consumo de alimentos (g), consumo de agua (ml), producción de heces (g), producción de orina (ml), peso corporal (g) y cambios (%), además actividades diarias (tiempo dedicado a la locomoción, búsqueda de alimento, y reposo). El tratamiento se realizó con tres repeticiones para 12 machos maduros y 12 hembras maduras no gestantes. Los análisis de experimentos de datos se realizaron con la prueba T. Resultados: Las ratas arroceras en la T-maze arena evitaron consumir alimentos y bebidas cercanos al extracto de metanol de hojas de Plumeria rubra. El tratamiento del extracto metanólico de hojas de Plumeria rubra en la prueba metaboliccage provocó un trastorno metabólico en estas ratas, lo cual se demostró significativamente en la disminución del consumo promedio de alimento en 2.28 g y la excreción de heces en 0.34 g, además en el aumento del consumo promedio de bebida en 3.89 ml, excreción de orina en 3.15 ml y peso corporal en 6.67 g. El tratamiento también provocó un trastorno en los patrones de actividad diaria de las ratas, lo cual fue demostrado por el aumento significativo en el porcentaje promedio de tiempo para actividades de movimiento (locomoción) en un 7.64 % y la disminución del tiempo para comer y beber (búsqueda de alimento) en un 16.46 %. Conclusión: El extracto metanólico de hojas de Plumeria rubra tiene un efecto repelente en las ratas arroceras.

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.

Effects of Siwu Decoction on Memory and Spatial Learning in Mice with Blood Deficiency and Related Mechanisms / 医药导报

Objective To investigate the effects of Siwu decoction on the learning and memory abilities in mice with blood deficiency and the related mechanism.Methods The mice were randomly divided into five groups:normal control group,model control group,high-,medium-,and low-dose group of Siwu decoction.Blood deficiency mouse model was established by continuously cuttingtailand bleedingin model control group,high-,medium-,and low-dose group of Siwu decoction.The mice in high-,medium-,and low-dose group were intragastrically administrated with Siwu decoction of 2.5,5.0,10.0 g·kg-1 for 14 days,respectively.The erythrocyte counts (RBC),hemoglobin (HGB),red blood cell hematocrit (HCT) were detected before modeling,7 and 14 days after administration.The spatial learning and memory abilities were assessed using the T maze test.The spontaneous activities were assessed using locomotors activity detector.The levels of erythropoietin (EPO) content in serum and acetylcholinesterase (AChE) in hippocampal tissue were detected by enzyme-linked immunousorbent assay.Results 5.0 and 10.0 g·kg-1Siwu decoction could increase RBC,HGB,HCT on the 7th and 14th day,2.5 g.kg-1Siwu decoction could increase RBC,HCT on 14th day,and each dosage of Siwu decoction could significantly increase the spontaneous activities of model mice with blood deficiency on the 7th and 14th day as compared with model control group (P ＜0.05 or P ＜0.01).Compared with model control group,the number of errorsin T Maze test were decreased significantly in high-,medium-,and low-dose groups (P ＜ 0.01).And the Siwu decoction had a tendency to reduce the hippocampal AChE levels,but when compared with the model control group there were no statistical differences (P ＞ 0.05).Conclusion Siwu decoction is benefit formemory and spatial learning in mice with blood deficiency,which may be related with higher serun EPO and lower hippocampal AChE expression.

Anxiolytic, Sedative and Hypothermic Effects of Aqueous Leaf Extract of Vernonia amygdalina Del. (Asteraceae) in Albino Mice.

Aims: This study evaluated the anxiolytic, sedative and hypothermic effects of aqueous leaf extract of Vernonia amygdalina in Mice. Study Design: One-factor two control groups experimental design. Place and Duration of Study: Department of Pharmacology, Faculty of Pharmacy, Obafemi Awolowo University, Ile-Ife, Osun State, Nigeria, between October 2012 and January 2013. Methodology: Animal models of novelty induced behaviours (rearing and locomotion), anxiolysis (T-maze and hole-board), sedation (amylobarbitone induced hypnosis) and hypothermia (rectal temperature measurement) were utilized in this study. Five different groups of white albino mice of both sexes weighing 23 – 28g (n=5 or 6) were randomly selected. Group 1 was the control (normal saline, 10 ml/kg, i.p.), group 2 was the positive control (diazepam, 1mg/kg, i.p.), while group 3, 4 and 5 were treated with aqueous leaf extract at 50, 100 and 200mg/kg, i.p., respectively. All animals in each group were pretreated for 30 minutes before assessment. Results: V. amygdalina at 50 mg/kg showed anxiolytic activity by significantly (P<0.001) increasing the frequency of head-dip compared to control, and also a significant (P =.05) decrease and increase (P<0.001) in latencies to withdrawal from the closed and open arms of the elevated T-maze respectively. However, at 100-200mg/kg, V. amygdalina showed sedative activity by significantly (P<0.001) decreasing rearing, locomotion (P<0.001) and head-dip frequency (P<0.001) in mice. Furthermore, V. amygdalina (100- 200mg/kg) caused significant (P<0.001) decrease in sleep latency and significantly (P<0.001) increased sleep duration in amylobarbitone-induced sleeping test indicating sedative activity. V. amygdalina (50-200mg/kg) also caused significant (at 30 min, 60 min, 90 min and 120 min; P=.05) reduction in rectal temperature in mice compared to normal saline and diazepam. Conclusion: The aqueous leaf extract of V. amygdalina may possess anxiolytic, sedative and hypothermic effects, hence justifying its folkloric medicinal use.

Evaluation of neurotransmitters involved in the anxiolytic and panicolytic effect of the aqueous fraction of Paullinia cupana (guaraná) in elevated T maze

This study investigated the effects of repeatedly administration of an aqueous fraction of Paullinia cupana Kunth, Sapindaceae (guaraná) seeds (8 mg/kg) on rats submitted to the elevated T-maze, model of generalized anxiety and panic disorders. The selective serotonin reuptake inhibitor paroxetine (3 mg/kg), was used as a positive control. To evaluate possible neurotransmissions involvement, ineffective doses of metergoline (3 mg/kg - non-selective serotonin receptor antagonist), sulpiride (20 mg/kg - non-selective dopaminergic receptor antagonist) or ketamine (0.125 mg/kg - non-selective glutamate receptor antagonist) were acutely administered in association with the aqueous fraction of P. cupana. Both aqueous fraction and paroxetine decrease the inhibitory avoidance latencies of the elevated T-maze, indicating anxiolytic effect and increased one-way escape latencies from the open arm of the elevated T-maze, indicating a panicolytic effect. The pre-treatment with metergoline, sulpiride and ketamine blocked the anxiolytic effect of aqueous fraction. The panicolytic effect of aqueous fraction was blocked by both metergoline and sulpiride. These results show that the serotonergic, dopaminergic and glutamatergic neurotransmission systems are involved in anxiolytic effect promoted by aqueous fraction, whereas only the serotonergic and the dopaminergic neurotransmission systems are involved in the panicolytic effect promoted by aqueous fraction of P. cupana. The effects produced by paroxetine, were blocked only by metergoline, validating this experimental procedure.

Effect of Food Deprivation on a Delayed Nonmatch-to-place T-maze Task

Food deprivation can affect performance on difficult cognitive task, such as the delayed nonmatch-to-place T-maze task (DNMT). The importance of food deprivation on maintaining high motivation for DNMT task has been emphasized, but not many studies have investigated the optimal conditions for depriving rodents to maximize performance. Establishing appropriate conditions for food deprivation is necessary to maintain DNMT task motivation. We applied different conditions of food deprivation (1-h food restriction vs. 1.5-g food restriction; single caging vs. group caging) and measured body weight and the number of correct choices that 8-week-old C57BL/6J mice made during the DNMT task. The 1.5-g food restriction group maintained 76.0+/-0.6% of their initial body weight, but the final body weight of the 1-h food restriction condition group was reduced to 62.2+/-0.8% of their initial body weight. These results propose that 1.5-g food restriction condition is effective condition for maintaining both body weight and motivation to complete the DNMT task.

The effects of swimming exercise on recognition memory for objects and conditioned fear in rats / Os efeitos do exercício de natação sobre a memória para reconhecimento de objetos e de medo condicionados em ratos

Experiments conducted in animals have repeatedly demonstrated the ability of exercise to enhance cognitive function. This study examines the effects of chronic swimming exercise on non-spatial memory in adult rats after 12 weeks of swimming exercise in object recognition and elevated T-maze tests. In the object recognition test, repeated measures analysis of variance revealed a group effect (F1,42 = 26,093; p < 0.001), control rats had lower discrimination ratios than the exercise group. However, the swimming exercise did not affect the performance of inhibitory avoidance and escapes, when memory was tested in elevated T-maze. Analysis of variance showed a significant reduction in inhibitory avoidance 24h after the first training (F1,42 = 14,552; p < 0.001). Results indicated that regular swimming exercise significantly increased non-spatial memory in object recognition behavior, but did not affect the performance of inhibitory avoidance and escape on elevated T-maze test in adult rats. These findings suggest that the perirhinal cortex plays a role in memory consolidation and storage in addition to that of the amygdala, which could be regarded as the center of a second memory system, separate from those governed by the perirhinal cortex.

As experiências realizadas em animais mostram a capacidade do exercício em melhorar as funções cognitivas. Este estudo analisa os efeitos do exercício crônico de natação sobre a memória não-espacial em ratos adultos após 12 semanas de exercício de natação nos testes de reconhecimento de objetos e labirinto em T elevado. O teste de reconhecimento de objetos, pelas repetidas análises de variância revelaram um efeito de grupo (F1,42 = 26.093; p < 0,001), os ratos controles discriminaram uma razão inferior ao do grupo de exercício. Entretanto, o exercício de natação não afetou o desempenho de esquiva inibitória e escape, quando a memória foi testada no labirinto em T elevado. Análise de variância mostrou redução significativa na esquiva inibitória 24h após o primeiro treino (F1,42 = 14.552; p < 0,001). Os resultados indicam que o exercício regular de natação aumenta significativamente a memória não-espacial no comportamento de reconhecimento de objetos, mas não afeta o medo condicionado no teste do labirinto em T elevado em ratos adultos. Estes resultados sugerem que o córtex peririnal desempenha papel nos processos de consolidação e armazenamento de memória além da amígdala, podendo esta ser encarada como um segundo centro de sistema de memória, separada dos regidos pelo córtex peririnal.

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.

Anxiolytic effects of repeated treatment with an essential oil from Lippia alba and (R)-(-)-carvone in the elevated T-maze

Lippia alba (Mill.) N.E. Brown (Verbenaceae) is widely used in different regions of Central and South America as a tranquilizer. The plant’s anxiolytic properties, however, merit investigation. The present study evaluated the effects of repeated daily (14 days) intraperitoneal (ip) treatment with an essential oil (EO) from a chemotype of L. alba (LA, chemotype II, 12.5 and 25 mg/kg; N = 6-8) and (R)-(-)-carvone (25 mg/kg; N = 8-12), the main constituent of this chemotype, on male Wistar rats (weighing 250 g at the beginning of the experiments) submitted to the elevated T-maze (ETM). The ETM allows the measurement of two defensive responses: inhibitory avoidance and one-way escape. In terms of psychopathology, these responses have been related to generalized anxiety and panic disorder, respectively. Treatment with the EO impaired ETM avoidance latencies, without altering escape, in a way similar to the reference drug diazepam (P < 0.05) (avoidance 2: control = 84.6 ± 35.2; EO 12.5 mg/kg = 11.8 ± 3.8; EO 25 mg/kg = 14.6 ± 2.7; diazepam = 7 ± 2.1). (R)-(-)-carvone also significantly altered this same response (P < 0.05; avoidance 1: control = 91.9 ± 31.5; carvone = 11.6 ± 1.8; diazepam = 8.1 ± 3.3). These results were not due to motor changes since no significant effects were detected in an open field. These observations suggest that LA exerts anxiolytic-like effects on a specific subset of defensive behaviors that have been implicated in generalized anxiety disorder, and suggest that carvone is one of the constituents of LA responsible for its action as a tranquilizer.

Relationship between novelty seeking phenotype and impulsive behavior in rats / 中华行为医学与脑科学杂志

ObjectiveTo investigate the relationship between novelty seeking and impulsivity behavior in rats.MethodsTwo models were used to test Novelty seeking,one was activity in a new environment model,the other was novel object preference model.And impulsivity was measured by T-maze.All rats(48) were used to examine the relationship between these two behaviour traits.ResultsNovelty seeking:the locomotor activities measured in a new environment for 30 min were (4695.58 ± 1579.87)cm,the exploring number of entries into the novel object area and time spending in the novel object area were respectively(20.92 ± 14.84)entries and (178.12± 135.22)s.Impulsivity:the average times of choosing low reward(LR) in the two test days were(4.71 ±2.71 ).Pearson product moment correlation was performed to investigate the relationship between these two behaviour traits,and the results suggested that there were notable correlation between novel object preference and impulsive decision making( r =0.295,P＜ 0.05 ),yet no significance were found between new environment activity and impulsive decision making.ConclusionNovelty seeking and impulsivity may be correlated with each other depending on different models.

Effects of chronic corticosterone and imipramine administration on panic and anxiety-related responses

It is known that chronic high levels of corticosterone (CORT) enhance aversive responses such as avoidance and contextual freezing. In contrast, chronic CORT does not alter defensive behavior induced by the exposure to a predator odor. Since different defense-related responses have been associated with specific anxiety disorders found in clinical settings, the observation that chronic CORT alters some defensive behaviors but not others might be relevant to the understanding of the neurobiology of anxiety. In the present study, we investigated the effects of chronic CORT administration (through surgical implantation of a 21-day release 200 mg pellet) on avoidance acquisition and escape expression by male Wistar rats (200 g in weight at the beginning of the experiments, N = 6-10/group) tested in the elevated T-maze (ETM). These defensive behaviors have been associated with generalized anxiety and panic disorder, respectively. Since the tricyclic antidepressant imipramine is successfully used to treat both conditions, the effects of combined treatment with chronic imipramine (15 mg, ip) and CORT were also investigated. Results showed that chronic CORT facilitated avoidance performance, an anxiogenic-like effect (P < 0.05), without changing escape responses. Imipramine significantly reversed the anxiogenic effect of CORT (P < 0.05), although the drug did not exhibit anxiolytic effects by itself. Confirming previous observations, imipramine inhibited escape responses, a panicolytic-like effect. Unlike chronic CORT, imipramine also decreased locomotor activity in an open field. These data suggest that chronic CORT specifically altered ETM avoidance, a fact that should be relevant to a better understanding of the physiopathology of generalized anxiety and panic disorder.

Effect of methylphenidate on enhancement of spatial learning by novel alternated dual task.

The novel alternated dual task (ADT) arranged rats to learn Tmaze spontaneous alternation task and radial arm maze (RAM) task alternatively, and by doing ADT, rats could acquire the tasks more easily than non alternated dual task (NADT) group. Also retention capacity of ADT group was significantly more and ADT help to learn a complex task faster than learning it in isolation from other tasks. In the present study effect of methylphenidate (MPD), a mood elevator, known to enhance learning and memory, on ADT procedure is assessed. Also effect of ADT procedure and MPD on spatial learning and memory are compared. Different groups were assigned by administering MPD (intraperitoneal injection at a dose of 3 mg/kg body weight) during different phases of behavioural experiments, and control groups received saline injection. MPD administration increased both acquisition and retention capacities. The amelioration attained for retention of complex task by ADT procedure, could be achieved by NADT rats only by administration of MPD. The influence of ADT procedure on acquisition and retention of TM and RAM tasks were similar to the effects of MPD, especially for the RAM task. MPD at low dose is found to enhance the learning and memory capacity in rats, than deteriorating it, supporting the use of MPD as a drug to treat attention deficit hyperactive disorder. The recent reports suggesting the effect of MPD only on retention and not on acquisition could not be confirmed, as enhancement for both acquisition and retention was found in this study.

Effects of reversible inactivation of the dorsomedial hypothalamus on panic- and anxiety-related responses in rats

The medial hypothalamus is part of a neurobiological substrate controlling defensive behavior. It has been shown that a hypothalamic nucleus, the dorsomedial hypothalamus (DMH), is involved in the regulation of escape, a defensive behavior related to panic attacks. The role played by the DMH in the organization of conditioned fear responses, however, is less clear. In the present study, we investigated the effects of reversible inactivation of the DMH with the GABA A agonist muscimol on inhibitory avoidance acquisition and escape expression by male Wistar rats (approximately 280 g in weight) tested in the elevated T-maze (ETM). In the ETM, inhibitory avoidance, a conditioned defensive response, has been associated with generalized anxiety disorder. Results showed that intra-DMH administration of the GABA A receptor agonist muscimol inhibited escape performance, suggesting an antipanic-like effect (P < 0.05), without changing inhibitory avoidance acquisition. Although a higher dose of muscimol (1.0 nmol/0.2 µL; N = 7) also altered locomotor activity in an open field when compared to control animals (0.2 µL saline; N = 13) (P < 0.05), the lower dose (0.5 nmol/0.2 µL; N = 12) of muscimol did not cause any motor impairment. These data corroborate previous evidence suggesting that the DMH is specifically involved in the modulation of escape. Dysfunction of this regulatory mechanism may be relevant in the genesis/maintenance of panic disorder.

The hypothalamic-pituitary-adrenal axis in anxiety and panic

This review article focuses on the differential activation of the hypothalamic-pituitary-adrenal (HPA) axis in generalized anxiety and panic. The results of experimental studies that assayed adrenocorticotropic hormone, cortisol and prolactin show that real-life panic attacks as well as those induced by selective panicogenic agents, such as lactate and carbon dioxide, do not activate the HPA axis. Accordingly, experiments carried out in two animal models of panic, namely electrical stimulation of the dorsal periaqueductal gray matter of the rat and the escape from the open arm of the elevated T maze, have shown that in neither case stress hormones are increased in the plasma. Also in humans, reported results have shown that neither cortisol nor prolactin levels were increased following simulated public speaking, an experimental task that has been related to panic, in either healthy volunteers or patients with panic disorder diagnosis. Therefore, although the panic attack causes a major sympathetic stimulation, it has little effect on the HPA axis. In contrast, anticipatory or generalized anxiety activates both the HPA and the sympatho-adrenal axes.

The effects of diazepam on the elevated T-maze are dependent on the estrous cycle of rats

In order to determine the modulation of anxiolytic and panicolytic-like effects of diazepam by the hormonal cycle of female rats, male and female rats - the latter divided per estrous cycle phase (estrus, diestrus, metaestrus and proestrus) - were tested in the elevated T-maze, a behavioral model of panic and anxiety. Diazepam (0.5, 1.0 and 2.0 mg/kg) or saline solution was injected in individual animals that were submitted to one session in the elevated T-maze 25 min after drug/saline administration. The test consisted of three avoidance trials and one escape trial, separated by a 30 s interval, during which the animals were isolated in individual cages. The avoidance trials began with the animal being placed at the end of the maze's enclosed arm. The time necessary for the animal to leave the central square was considered as the response's latency. The trials that exceeded 300 s were considered as failures. Results demonstrate a decrease in the effects of diazepam in inhibitory avoidance (anxiety) trials in females in diestrus and proestrus, but no relation of gender or estrous cycle on diazepam effects on escape trials (fear). The results support the hypothesis that down-regulation of GABA A receptors by activation of nuclear estrogen receptors and induction of PKC-mediated GABA A receptor phosphorylation by activation of surface estrogen receptors in raphe neurons underlie the modulation of diazepam sensitivity by estrogen.

Evaluation of allocentric spatial learning in rats using a novel “Alternated Dual Task”.

Allocentric spatial learning can be assessed using popular spontaneous alternation behaviour (SAB) tested with T-maze, and also using radial arm maze (RAM) tasks. But the SAB testing has been reported to have lack of validity as a measure of retention, especially when used as a measure of short term memory. A more complex dual alternated task was designed to clarify whether increasing novelty and alternation factors in a task will increase or decrease the short term and long term memory in rats. Rats were made to learn both T-maze spontaneous alternation task and RAM task alternatively. Another group of rats were made to learn both the task separately without any alternation. And control group of rats were assigned to learn only one type of task. It was found that the group of rats performing “alternated dual task” could acquire the tasks more easily than the control groups and non alternated dual task groups. This enhancement of acquisition was associated only with the complex task (RAM task) among the dual tasks. More over their retention (memory) ability was very significantly enhanced for both the tasks in dual tasks. It can be concluded that, the principle of “alternated dual task” can be made use when a complex task has to be acquired and learned faster by rats; as alternation with simple task enhances the ability of rats to learn and memorize a complex task more efficiently.

The effect of apomorphine on visual discrimination learning and reversal learning in rats / 中华行为医学与脑科学杂志

Objective Using apomorphine, a potent dopamine receptor agonist and rotating T-maze, the effect of apomorphine on the visual discrimination learning and reversal learning in rats was investigated. Methods All rats were trained in a visual discrimination task (food reward and light stimulus) in rotating T-maze. After reaching the acquisition criterion, rats were trained in a reversal task (food reward and without light stimulus) in the same maze. During the period of visual discrimination task, apomorphine was administrated either 30 minutes prior to learning or after learning immediately. Results The results showed that apomorphine, which was given either 30 minutes prior to visual discrimination learning or after learning, could impair the acquisition of discrimination learning( 259.20±26.29 and 264.00±16.97, compared to 168.00±16.97 and 163.20±20.08) and apomorphine, which was given only after visual discrimination learning, could impair the acquisition of reversal learning (451.20±39.44 compared to 360.00±29.39). Conclusion The results showed that apomorphine, which was given either 30 minutes prior to visual discrimination learning or after learning, could impair the acquisition of discrimination learning and apomorphine, which was given only after visual discrimination learning, could impair the acquisition of reversal learning.

Evaluation of the effects of photooxidized Echis carinatus venom on learning, memory and stress

Snake venoms are a mixture of complex proteins, which have many physical and pharmacological properties. Photochemical detoxification has been suggested to generate photooxidized Echis carinatus venom product (POECVP). Antigenically-active photooxidized species of Echis carinatus venom could be obtained by exposing the venom to ultraviolet radiation (UVR) in the presence of methylene blue. The aim of the present study was to evaluate the effects of POECVP on learning, memory and stress in rats. Detoxification of the photooxidized venom was evident since the POECVP-treated group had longer survival time than the group of mice treated with Echis carinatus venom product (ECVP) following intraperitoneal and intracerebral injections. Photooxidized Echis carinatus venom product showed antidepressant activity by prolonging sleep onset and shortening the duration of pentobarbitone-induced hypnosis in mice. In single and chronic dose studies with rats, we observed that POECVP significantly decreased the time needed to reach food in T-maze, shortened transfer latency in elevated plus-maze, and decreased immobility time in forced swim test. We concluded that although there is a possibility of employing POECVP in the treatment of depressive and chronic degenerative illnesses as a nonherbal and nonsynthetic alternative for patients not responding to the available therapy, further investigation is still needed.(AU)

Effect of Ethanol on Short-term Memory in Rats:A Mechanism of Alcoholic Dementia

Chronic and excessive alcohol consumption produces a subtle brain damage, which induces such organic mental disorders as delayed mental processes, abstract thinking impairment, and disturbances in learning and recent memory loss. These phenomena had been known to be caused by malnutrition. However, recent researches showed that it could be caused by mild brain lesions by direct neurotoxic effect of alcohol on the prefrontal cortex, or its related subcortical structures. This study was tried to evaluate the effect of alcohol on the short-term memory function, to compare with the histological changes, and to find out responses to the agonists and antagonists of possibly related neurotransmitters. For experiment 1, 10 aged male Sprague-Dawley rats weighed about 400-500 gm were used. 45 younger adult male Sprague-Dawley rats weighed about 200-300 gm were used for experiment 2 and 3. Therefore, 55 rats were totally used. In experiment 1, T-maze test with 10 nomal aged rats were done first, and then it was divided into 5 atropine-administered group and 5 control group. For the atropine-administered group, T-maze test was repeated on every 30, 60, 120 minute after the atropine injection. After the completion, of behavioral tests, the rats were sacrificed by the intracardiac perfusion with phosphate buffered 10% formaldehyde solution, and the brain specimen was stained with hematoxylin-eosin to count cells in the prefrontal cortex and the hippocampus. In experiment 2, T-maze test with 10 normal younger adult rats were done first, and then it was dividied into five 14% (v/v) ethanol administered group and 5 control group raised with tap water. T-maze test was repeated on every week for a month. After the completion of behavioral tests on the 4th week, histology was done by the same procedure. In experiment 3, T-maze test with 35 normal younger adult rats were done first, and then it was divided into seven groups with five rats each other. 14% (v/v) ethanol was administered ad libitum. In addition, normal saline, fluoxetine, bromocriptine, bethacholine, nimodipine, clonidine, and ketamine were intramuscularly injected on every other day. T-maze test was repeated on every week for a month. After the completion of behavioral tests on the 4th week, histology was done by the same procedure. 1) The reaction time of T-maze test was more delayed on 120 minutes after atropine injection in atropine-administered rats than those in normal aged rats without statistical significance. 2) The reaction time of T-maze test was more delayed in ethanol-treated rats, especially most prominent on the 3rd week, than those in normal younger adult rats without statistical significance. However, cell numbers in the CA1, CA3, dentate gyrus and the prefrontal cortex were significantly reduced in ethanol-treated rats on histology (p<0.05). 3) The reaction time of T-maze test was more shortened in fluoxetine and ketamine-treated rats on the 1st week without statistical significance. It was rather shortened in fluoxetine, ketamine, bromocriptine and nimodipine-treated rats without statistical significance on the 2nd week. On the 3rd week, the reaction time of T-maze test was shortened in every drug-treated rats. It returned to be delayed in all but fluoxetine, clonidine and bethacholine-treated rats on the 4th week without statistical significance. However, cell numbers in the CA1 were significantly increased in bromocriptine-treated rats (p<0.05) and in bethacholine-treated rats (p<0.01). In the CA3 and the dentate gyrus, cell numbers in bethacholine and clonidine-treated rats were significantly increased (p<0.05 respectively). In the prefrontal cortex, cell numbers in bethacholine-treated rats were significantly increased (p<0.005) on histology. 4) While there were no significant difference on the reaction time of T-maze test between ethanol-treated group, normal aged group and atropine-treated group, cell numbers in the prefrontal cortex were significantly different between those of normal aged group and atropine-treated group (p<0.05). Cell numbers in the prefrontal cortex of ethanol-treated group were signifncantly correlated with those of atropine-treated group (r=0.977, p<0.001), and of normal aged group (r=0.448, p<0.05). In conclusion, we should not neglect the risk of memory loss even in the subclinical cases, because neuronal cells in the prefrontal cortex and the hippocampus were significantly reduced on histology, while ethanol-induced short-term memory loss was not functionally significant. The drug responses in this experiments showed that the mechanism of alcohol-induced short-term memory loss might be mainly related with cholinergic system. Otherwise, adrenergic or dopaminergic mechanisms could be involved. Furthermore, we could not exclude the possiblity that pathological aging process might be exerted as an important mechanism underlying alcoholic dementia.