We Were There:Experiences of women in the Maze and Long Kesh Prison

A feature documentary on the experiences of women in the Maze and Long Kesh Prison

Anxiolytic-like effects observed in rats exposed to the elevated zero-maze following treatment with 5-HT2/5-HT3/5-HT4 ligands

The present study examined the effects of administering selective 5-HT antagonists and agonists to rats tested in the elevated zero-maze (EZM) model of anxiety. The EZM paradigm has advantages over the elevated plus-maze (EPM) paradigm with respect to measuring anxiety, yet has been utilized less frequently. Three experiments were conducted each with a diazepam control (0.25, 0.5 and 0.75 mg/kg). In the first experiment, we administered the 5-HT_2C antagonist RS 102221 (0.5, 1.0, and 2.0 mg/kg) and 5-HT_2C agonist MK-212 (0.25, 0.5 and 0.75 mg/kg); in the second experiment, we administered the 5-HT₃ antagonist Y-25130 (0.1, 1.0 and 3.0 mg/kg) and 5-HT₃ agonist SR 57227A (0.1, 1.0 and 3.0 mg/kg), and in the third experiment, we administered the 5-HT₄ antagonist RS 39604 (0.01, 0.1, 1.0 mg/kg) and 5-HT₄ agonist RS 67333 (0.01, 0.1 and 0.5 mg/kg). The administration of 5-HT_2/3/4 subtype antagonists all generated behavioral profiles indicative of anxiolytic-like effects in the EZM, which was apparent from examination of both traditional and ethological measures. While little effect was observed from 5-HT₂ and 5-HT₃ agonists, the 5-HT₄ agonist RS 67333 was found to produce a paradoxical anxiolytic-like effect similar to that produced by the 5-HT₄ antagonist RS 39604. We conclude by discussing the implications of these findings.

Integration of olfactory information in a spatial representation enabling accurate arm choice in the radial arm maze

The aim of the present study was to determine whether and how rats can use local olfactory cues for spatial orientation. Rats were trained in an eight-arm radial maze under different conditions as defined by the presence or absence of supplementary olfactory cues marking each arm, the availability of distant visuospatial information, and the illumination of the maze (light or darkness). The different visual conditions were designed to dissociate among the effects of light per se and those of visuospatial cues, on the use of olfactory cues for accurate arm choice. Different procedures with modifications of the arrangement of olfactory cues were used to determine if rats formed a representation of the spatial configuration of the olfactory cues and if they could rely on such a representation for accurate arm choice in the radial maze. The present study demonstrated that the use of olfactory cues to direct arm choice in the radial arm maze was critically dependent on the illumination conditions and implied two different modes of processing of olfactory information according to the presence or the absence of light. Olfactory cues were used in an explicit manner and enabled accurate arm choice only in the absence of light. Rats, however, had an implicit memory of the location of the olfactory cues and formed a representation of the spatial position of these cues, whatever the lighting conditions. They did not memorize the spatial configuration of the olfactory cues per se but needed these cues to be linked to the external spatial frame of reference.

GPR30 activation decreases anxiety in the open field test but not in the elevated plus maze test in female mice

The GPR30 is a novel estrogen receptor (ER) that is a candidate membrane ER based on its binding to 17beta estradiol and its rapid signaling properties such as activation of the extracellular-regulated kinase (ERK) pathway. Its distribution in the mouse limbic system predicts a role for this receptor in the estrogenic modulation of anxiety behaviors in the mouse. A previous study showed that chronic administration of a selective agonist to the GPR30 receptor, G-1, in the female rat can improve spatial memory, suggesting that GPR30 plays a role in hippocampal-dependent cognition. In this study, we investigated the effect of a similar chronic administration of G-1 on behaviors that denote anxiety in adult ovariectomized female mice, using the elevated plus maze (EPM) and the open field test as well as the activation of the ERK pathway in the hippocampus. Although estradiol benzoate had no effect on behaviors in the EPM or the open field, G-1 had an anxiolytic effect solely in the open field that was independent of ERK signaling in either the ventral or dorsal hippocampus. Such an anxiolytic effect may underlie the ability of G-1 to increase spatial memory, by acting on the hippocampus.

Efeito da administração crônica pós-natal dos ácidos propiônico e metilmalônico sobre o comportamento de ratos no labirinto aquático de Morris (Water Maze) e sobre alguns parâmetros bioquímicos de estresse oxidativo em hipocampo

As acidemias propiônica e metilmalônica são desordens neurometabólicas hereditárias caracterizadas por progressiva deterioração neurológica, retardo mental, atraso no desenvolvimento psicomotor, convulsões e coma. A fisiopatologia do dano cerebral característico destas doenças ainda é pouco conhecida. No presente estudo investigamos o efeito de administração crônica (5o ao 28o dia de vida) dos ácidos propiônico (PA) e metilmalônico (MA), que são os metabólitos acumulados em maiores concentrações nos pacientes portadores das acidemias propiônica e metilmalônica, respectivamente, sobre o comportamento de ratos e sobre alguns parâmetros bioquímicos de estresse oxidativo no hipocampo dos animais. O comportamento dos animais foi avaliado 30 dias após o término do tratamento nas tarefas do labirinto aquático de Morris e no campo aberto. Os parâmetros bioquímicos avaliados foram o potencial antioxidante total do tecido (TRAP) e a atividade das enzimas catalase, superóxido dismutase e glutationa redutase. Todos as análises bioquímicas foram realizadas em hipocampo, estrutura fundamental para a localização espacial, requerida na tarefa do labirinto aquático de Morris. As doses de propionato ou metilmalonato foram administradas de acordo com as preconizadas nos modelos experimentais destas acidemias, tomando em consideração o peso e da idade dos animais. Os ratos controles receberam solução salina nos mesmos volumes. A administração de PA ou MA não alterou o peso dos animais. Entretanto foi encontrado um déficit de aprendizado e memória no grupo tratado com PA, e um déficit de memória no grupo tratado com MA. Nenhum dos grupos testados apresentou alterações na atividade motora (número de cruzamentos) na tarefa do campo aberto. Também determinamos o efeito da co-administração de ácido ascórbico nos animais tratados cronicamente com PA ou MA. Encontramos que o ácido ascórbico preveniu o déficit cognitivo provocado pela administração crônica de PA e MA. Por outro lado, verificamos que os tratamentos crônicos com PA e MA diminuíram o TRAP no hipocampo dos ratos, sem alterar a atividade de nenhuma das enzimas testadas. A prevenção do déficit cognitivo pelo ácido ascórbico associada à diminuição do TRAP no hipocampo dos animais tratados cronicamente com PA ou MA sugere que o estresse oxidativo pode estar relacionado com o déficit cognitivo encontrado no presente trabalho. Concluindo, nossos resultados indicam que o estresse oxidativo pode estar envolvido, ao menos em parte, com o dano cerebral nos pacientes afetados pelas acidemias propiônica e metilmalônica.

Longitudinal study of daily variation of rats' behavior in the elevated plus-maze

We conducted a longitudinal study about daily variation of Wistar male rats' behavior in the elevated plus-maze (EPM) evaluated in the 1st, 2nd, 3rd, 6th, 12th, and 18th months of life. Animals were submitted to the plus-maze in 12 sessions at 2-h intervals (n=72, 6 per time point). Spontaneous rest-activity rhythm of four animals was assessed by observation of 24-h videotape records. Time series were analyzed by Cosinor method. Behavioral rates on the six occasions and in light and dark phases were compared by means of two-way ANOVA with repeated measures. Exploratory behavior in EPM was smaller in the light phase and in older animals. Higher values of open and closed arms exploration were observed in the first and third months of the dark phase, and in the first month of the light phase. Adjustment to the 24-h period was significant at all stages for rest-activity data, number of entries in closed arms, and time on center, and for three to five stages for open-arm exploration. In general, 24 h variability was more pronounced in younger animals compared with older ones. The present study showed that: (1) a significant amount of total variability of the behavioral indexes analyzed could be attributed to 24 h variation, (2) light/dark phases differences in EPM exploration were present at all developmental stages, (3) older Wistar rats explored less the EPM and were less active in their home cage compared with younger ones, and (4) behavioral indexes (EPM) decrease was phase related and partially related to a reorganization of rest-activity rhythm. (C) 2003 Elsevier B.V. All rights reserved.

Serotonergic neurons in the median raphe nucleus regulate inhibitory avoidance but not escape behavior in the rat elevated T-maze test of anxiety

Rationale: A wealth of evidence supports the involvement of the serotonergic neurons of the median raphe nucleus (MRN) in anxiety. However, it is presently unclear whether serotonergic pathways arising from this nucleus play distinguishing regulatory roles in defensive behaviors that have been associated with specific subtypes of anxiety disorders. Objectives: To evaluate the role of the MRN serotonergic neurons in the regulation of two defensive behaviors, inhibitory avoidance and escape, which have been related, respectively, to generalized anxiety and panic disorders. Methods: Male Wistar rats were submitted to the elevated T-maze test of anxiety after intra-MRN administration of drugs that either non-selectively or selectively change the activity of the serotonergic neurons. Results: Intra-MRN injection of FG 7142 (0.04 and 0.08 nmol) and kainic acid (0.03 and 0.06 nmol), drugs that non-selectively stimulate the MRN serotonergic neurons, facilitated inhibitory avoidance acquisition, but impaired escape performance. Microinjection of muscimol (0.11 and 0.22 nmol), a compound that non-selectively inhibits the activity of the MRN serotonergic neurons, impaired inhibitory avoidance and facilitated escape performance. Both kainic acid and muscimol also changed rat locomotion in the open-field test. Intra-MRN injection of 8-OH-DPAT (0.6-15 nmol) and WAY-100635 (0.18-0.74 nmol), respectively an agonist and an antagonist of somatodendritic 5-HT1A receptors located on serotonergic neurons of the MRN, only affected inhibitory avoidance-while the former inhibited the acquisition of this behavior, the latter facilitated it. Conclusion: MRN serotonergic neurons seem to be selectively involved in the regulation of inhibitory avoidance in the elevated T-maze. This result supports the proposal that 5-HT pathways departing from this nucleus play an important role in anxiety processing, with implications for pathologies such as generalized anxiety disorder.

Social separation and diazepam withdrawal increase anxiety in the elevated plus-maze and serotonin turnover in the median raphe and hippocampus

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Evaluation of the elevated T-maze as an animal model of anxiety in the mouse

The elevated T-maze has been developed as an animal model of anxiety to generate both conditioned and unconditioned fears in the same rat. This study explores a version of the elevated T-maze fit for mice. Inhibitory (passive) avoidance-conditioned fear-is measured by recording the latency to leave the enclosed arm during three consecutive trials. One-way escape-unconditioned fear-is measured by recording the time to withdraw from open arms. The results showed that mice do not appear to acquire inhibitory avoidance in the standard T-maze, since their latencies to leave enclosed arm did not increase along trials. Nevertheless, the open arms seemed to be aversive for mice, because the latency to leave the enclosed arm after the first trial was lower in a T-maze with the three enclosed arms than in the standard elevated T-maze, In agreement, the exposure of mice to an elevated T-maze without shield, that reduces the perception of openness, increased significantly the latencies to leave the enclosed arm, However, the absence of the shield also increased the time taken to leave the open arms when compared to that recorded in standard T-maze. Systematic observation of behavioral items in the enclosed arm has shown that risk assessment behavior decreases along trials while freezing increases. In the open arms, freezing did not appear to influence the high latency to leave this compartment, since mice spend only about 8% of their time exhibiting this behavior, These results suggest that mice acquire inhibitory avoidance of the open arms by decreasing and increasing time in risk assessment and freezing, respectively, along three consecutive trials, However, one-way escape could not be characterized. Therefore, there are important differences between mice (present results) and rats (previously reported results) in the performance of behavioral tasks in the elevated T-maze. (C) 1999 Elsevier B.V.

Effects of intra-hippocampal infusion of WAY-100635 on plus-maze behavior in mice - Influence of site of injection and prior test experience

The positive profile of systemically-administered 5-HT(1A) receptor antagonists in several rodent models of anxiolytic activity suggests an important role for postsynaptic 5-HT(1A) receptor mechanisms in anxiety. To test this hypothesis, we investigated the effects of WAY-100635 microinfusions (0, 0.1, 1.0 or 3.0 mug in 0.2 mul) into the dorsal (DH) or ventral (VH) hippocampus an behaviours displayed by male Swiss-Webster mice in the elevated plus-maze. As prior experience is known to modify pharmacological responses in this test, the effects of intra-hippocampal infusions were examined both in maze-naive and maze-experienced subjects. Test videotapes were scored for conventional indices of anxiety (% open arm entries/time) and locomotor activity (closed arm entries), as well as a range of ethological measures (e.g. risk assessment). In maze-naive mice, intra-VH (but not intra-M) infusions of WAY-100635 (3.0 mug but not lower doses) increased open arm exploration and reduced risk assessment. These effects were observed in the absence of significant changes in locomotor activity. In contrast, neither intra-VH nor intra-DH infusions of WAY-100635 altered the behaviour of maze-experienced mice. These Findings suggest that postsynaptic 5-HT(1A) receptors in the ventral (but not dorsal) hippocampus play a significant role both in the mediation of plus-maze anxiety in mice and in experientially-induced alterations in responses to this test. (C) 2002 Elsevier B.V. BY All rights reserved.