Effects of chronic treatment with corticosterone and imipramine on fos immunoreactivity and adult hippocampal neurogenesis.

In a previous study we showed that rats chronically treated with corticosterone (CORT) display anxiogenic behavior, evidenced by facilitation of avoidance responses in the elevated T-maze (ETM) model of anxiety. Treatment with the tricyclic antidepressant imipramine significantly reversed the anxiogenic effects of CORT, while inhibiting ETM escape, a response related to panic disorder. To better understand the neurobiological mechanisms underlying these behavioral effects, analysis of c-fos protein immunoreactivity (fos-ir) was used here to map areas activated by chronic CORT (200 mg pellets, 21-day release) and imipramine (15 mg/kg, IP) administration. We also evaluated the number of cells expressing the neurogenesis marker doublecortin (DCX) in the hippocampus and measured plasma CORT levels on the 21st day of treatment. Results showed that CORT increased fos-ir in the ventrolateral septum, medial amygdala and paraventricular hypothalamic nucleus and decreased fos-ir in the lateral periaqueductal gray. Imipramine, on the other hand, increased fos-ir in the medial amygdala and decreased fos-ir in the anterior hypothalamus. CORT also decreased the number of DCX-positive cells in the ventral and dorsal hippocampus, an effect antagonized by imipramine. CORT levels were significantly higher after treatment. These data suggest that the behavioral effects of CORT and imipramine are mediated through specific, at times overlapping, neuronal circuits, which might be of relevance to a better understanding of the physiopathology of generalized anxiety and panic disorder.

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.

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.

Haloperidol and chlorpheniramine interaction in inhibitory avoidance in goldfish.

The purpose of this study was to investigate a possible interaction between histaminergic and dopaminergic systems in learning and memory processes, in an inhibitory avoidance test in goldfish. Haloperidol, a dopaminergic antagonist, was administrated pre-training and the chlorpheniramine (CPA), a histaminergic antagonist, post-training. The inhibitory avoidance procedure was performed in 3 days, using a rectangular aquarium divided into two compartments (black and white), with a central door. On the first day, the animals were habituated for 10 min. On the second day, they were injected with 2 mg/kg of haloperidol or dimethyl sulfoxide (DMSO) 20 min before training. Then, the animals were placed in the white compartment, the central door was opened and the time spent for crossing between compartments was recorded. After the fish crossed the line between compartments a 45 g weight was dropped. This procedure was done five times in a row. Immediately after the fifth trial, the fish were injected intraperitoneally (i.p.) with either saline or CPA (0.4, 1.0, 4.0, 8.0 or 16 mg/kg). On the next day (test) the time to cross was recorded again. On the training trials, the animals treated with DMSO or haloperidol presented a significant increase in the latencies indicating learning (Friedman P = 0.0062 and 0.0001). The latencies in the test day showed that groups pre-treated with haloperidol and treated with CPA presented a dose-dependent increase in latencies, and those treated with the 16 mg/kg CPA group showed a significant increase (ANOVA two-way followed by Student-Newman-Keuls (SNK) P < 0.01). Thus, it can be suggested that the facilitatory action occurs due to an additive interaction between both systems, in a dose-dependent way.

Comparacao de dois protocolos de fortalecimento para preensao plamar / Comparison of two protocols for increasing grip strength

A medida da forca de preensao palmar tem sido um dos meios uteis para a avaliacao das caracteristicas fisicas, a evolucao durante a reabilitacao e o grau de incapacidade. Na pratica clinica o fisioterapeuta se depara com a dificuldade em selecionar o protocolo mais adequado e eficiente para o fortalecimento muscular. O objetivo deste trabalho foi comparar dois protocolos de regimes isotonicos buscando evidenciar qual deles seria o mais indicado para o fortalecimento musculos responsaveis pela preensao. As medidas da forca de preensao pre e pos-treinamento foram realizadas com um dinamometro mecanico da marca Jamar, em 22 mulheres com idade entre 18 e 21 anos (media de 19 anos). As voluntarias foram separadas em 2 grupos, DeLorme (carga crescente) e Oxford (carga decrescente), para a aplicacao dos protocolos. Para o treinamento foi utilizado um exercitador de mao e dedos da marca Digi-flex, e o programa foi realizado duas vezes por semana, com duracao de 20 minutos cada sessao em um total de 8 sessoes. Posteriormente, foram comparadas as forcas pre e pos-treinamentos e foi observado que, para as amostras dependentes (pre e pos-treinamentos), houve diferenca significativa tanto no grupo DeLorme quanto no Oxford, ja para as amostras independentes (pos-DeLorme e pos-Oxford) nao houve diferenca significativa

Analysis of the effects of CPA and L-histidine on goldfish tested on a conditioned place preference model.

The aim of this study was to investigate whether the histamine H(1)- receptor blocker chlorpheniramine (CPA) and the histaminergic precursor L-histidine have reinforcing effects in goldfish (Carassius auratus). We used a place-preference procedure in a four-compartment aquarium in which, on the first day, the animals were placed for 30 min for habituation. On the second day, the time spent in each chamber was recorded for 10 min in order to determine which was preferred. After 24 h a non-transparent acrylic division was placed in the aquarium to make four identical compartments. The fish were injected intraperotoneally (i.p.) with L-histidine in three doses: 100, 250, and 500 mg/kg of body-weight (n=20) and with vehicle control (n=20). After 30 min the animals were placed in the intermediate preference chamber for another 30 min. The CPA was injected i.p in four doses; 0.4, 1.0, 4.0 or 8.0 mg/kg (n=16) or vehicle (n=16) and after 5 min the animals were placed in the intermediate preference chamber for another 30 min. On the fourth day the procedure of the second day was repeated. The results indicate that the group treated with 500 mg/kg L-histidine spent significantly more time in the paired compartment when compared with the time spent before treatment (Wilcoxon Signed Rank Test, P=0.0172). The same behavior was not observed in other treatment groups (P>0.05). The results indicate a reinforcing effect of L-histidine in this place preference model with goldfish.

Analysis of the role of histamine in inhibitory avoidance in goldfish.

1. Teleost fish have histaminergic cell bodies on the posterior part of the basal hypothalamus. It was suggested that they are homologous to the tuberomammillary E group in rats. However, unlike in rats, fish have fewer ascending fibers. The main projection runs through the ventral telencephalic area reaching the dorsal telencephalon. This projection is considered homologous to the prosencephalic forebrain bundle. 2. The aim of this study was to verify if the histaminergic system has an inhibitory action on learning and memory in goldfish, as suggested previously for higher vertebrates. 3. A two-compartment aquarium with a central sliding door was used. The animals were placed in one of them, the central door was opened after 30 sec and the time spend for crossing between compartments was recorded. After the fish dorsal fin crossed the line between the compartments a 45 g weight was dropped into the compartment the fish entered. 4. On the training day this procedure was done 3 times. Immediately after the 3rd trial the fish was injected i.p. with either vehicle (2 ml/kg), chlorpheniramine (CPA; 1.0, 4.0 and 8.0 mg/kg) or histidine (500 mg/kg). On the next day, fishes were placed in the start compartment and the latency to cross between compartments was again recorded. 5. The group treated with CPA at the dose of 8 mg/kg, presented a significant increase in the latency to leave the start compartment (Wilcoxon rank sum test, p<0.0232). On the other hand, the vehicle and 1-histidine (500 mg/kg) treated groups, presented a decrease in test latency. 6. Thus, we suggest that also in fish, the histaminergic system has an inhibitory role on learning and memory.

Natural preference of zebrafish (Danio rerio) for a dark environment.

The zebrafish (Danio rerio) has been used as a model in neuroscience but knowledge about its behavior is limited. The aim of this study was to determine the preference of this fish species for a dark or light environment. Initially we used a place preference test and in a second experiment we applied an exit latency test. A two-chamber aquarium was used for the preference test. The aquarium consisted of a black chamber and a white chamber. In the first experiment the animal was placed in the aquarium and the time spent in the two compartments was recorded for 10 min. More time was spent in the black compartment (Wilcoxon matched-pairs signed-rank test, T = 7, N1 = N2 = 18, P = 0.0001). In the second experiment the animal was placed in the black or white compartment and the time it took to go from the initial compartment to the opposite one was recorded. The test lasted a maximum of 10 min. The results showed that the animal spent more time to go from the black to the white compartment (Mann-Whitney rank sum test, T = 48, N1 = 9, N2 = 8, P<0.0230). These data suggest that this fish species has a natural preference for a dark environment and this characteristic can be very useful for the development of new behavioral paradigms for fish.

Natural preference of zebrafish (Danio rerio) for a dark environment

The zebrafish (Danio rerio) has been used as a model in neuroscience but knowledge about its behavior is limited. The aim of this study was to determine the preference of this fish species for a dark or light environment. Initially we used a place preference test and in a second experiment we applied an exit latency test. A two-chamber aquarium was used for the preference test. The aquarium consisted of a black chamber and a white chamber. In the first experiment the animal was placed in the aquarium and the time spent in the two compartments was recorded for 10 min. More time was spent in the black compartment (Wilcoxon matched-pairs signed-rank test, T = 7, N1 = N2 = 18, P = 0.0001). In the second experiment the animal was placed in the black or white compartment and the time it took to go from the initial compartment to the opposite one was recorded. The test lasted a maximum of 10 min. The results showed that the animal spent more time to go from the black to the white compartment (Mann-Whitney rank sum test, T = 48, N1 = 9, N2 = 8, P<0.0230). These data suggest that this fish species has a natural preference for a dark environment and this characteristic can be very useful for the development of new behavioral paradigms for fish.