Intracerebellar microinjection of histaminergic compounds on locomotor and exploratory behaviors in mice.

The neural histaminergic system innervates the cerebellum, with a high density of fibers in the vermis and flocculus. The cerebellum participates in motor functions, but the role of the histaminergic system in this function is unclear. In the present study, we investigated the effects of intracerebellar histamine injections and H1, H2 and H3 receptor antagonist injections (chlorpheniramine, ranitidine, and thioperamide, respectively) and H4 receptor agonist (VUF-8430) on locomotor and exploratory behaviors in mice. The cerebellar vermis of male mice was implanted with guide cannula. After three days of recovery,the animals received microinjections of saline or histamine (experiment1), saline or chlorpheniramine (experiment 2), saline or ranitidine(experiment 3), saline or thioperamide (experiment 4), and saline or VUF-8430 (experiment 5) in different concentrations. Five minutes postinjection,the open field test was performed. The data were analyzed using one-way ANOVA and Duncan's post hoc test. The microinjections of histamine, ranitidine or thioperamide did not lead any behavioral effects at the used doses. In contrast, animals that received chlorpheniramine at the highest dose (0.16 nmol) and VUF-8430 at the highest dose (1.48 nmol)were more active in the open field apparatus, with an increase in the number of crossed quadrants, number of rearings and time spent in the central area of the arena, suggesting that chlorpheniramine and VUF-8430 modulates locomotor and exploratory behaviors in mice.

Intracerebellar vermis histamine facilitates memory consolidation in the elevated T maze model.

Experimental evidence suggests that the cerebellum plays a more complex role in learning than simply regulating the motor response. Rather, it is thought to play a significant role in the consolidation of emotional memory in mice. Due to the difficulty of interpreting fear and anxiety behaviors-the standard methodology for the study of the histaminergic system and emotional memory-in mice, we propose a behavioral assessment of mice subjected to the Elevated T-maze after histamine microinjection of the cerebellar vermis. Young male Swiss albino mice weighing 25-35g were used. In addition, locomotor activity was tested in an open field test. Our data suggest that histamine did not affect memory consolidation during escape or open field behavior at the doses used in this study. However, we observed a significant increase in inhibitory avoidance on the second day in animals receiving a dose of 6.8nmol/0.5µl, suggesting that histamine facilitates the consolidation of inhibitory avoidance in mice.

Impairment in the aversive memory of mice in the inhibitory avoidance task but not in the elevated plus maze through intra-amygdala injections of histamine.

RATIONALE: Evidence indicates that histamine (HA) modulates learning and memory in different types of behavioral tasks; however, the exact nature of this modulation and its mechanisms are controversial. Furthermore, emotions are able to influence memory processing in a crucial way through the involvement of the amygdala. Our research aims to contribute to the neurobiological body of knowledge on acquisition and retrieval of emotional memory via the histaminergic amygdaloid system in mice. OBJECTIVES: The present study investigated whether exogenous HA infused into the amygdala differentially modulates the anxiety- and fear-related memory of mice assessed by unconditioned and conditioned tasks. METHODS: Over two consecutive days, animals received bilateral microinjections of either vehicle or HA (0.1, 0.5 and 1.0µg by 0.1µl/side volume) into the amygdala before behavioral tests were performed. Mice were examined under two paradigms: an exposure/re-exposure procedure in the elevated plus-maze (EPM) or in the inhibitory avoidance (IA) with electric foot shock trials 1 and 2 and retention test (without foot shock). RESULTS: Pre-test intra-amygdala microinjection of 0.5µg HA induced anxiolytic-like responses, but none of the three doses interfered in mnemonic processing examined in the EPM. Concerning the IA task, step-through retention latencies increased in all groups compared with their respective trials, except in the animals microinjected with 0.5 or 1.0µg HA before the retention test. Thus, HA caused statistically significant amnesia during the session repeated 24h after training without drugs. Retention latency was not modified by microinjections of HA both pre-trial and pre-test or by pre-trial infusion in mice subjected to IA. CONCLUSIONS: Our data indicate that the amygdaloid histaminergic system could modulate anxiety-related behaviors in the EPM and impair the retrieval process in fear conditioning with a strong aversive stimulus. These results contribute further evidence of the distinct histaminergic influence on different emotional pathways.

Muscle atrophy, voluntary activation disturbances, and low serum concentrations of IGF-1 and IGFBP-3 are associated with weakness in people with chronic stroke.

BACKGROUND: The muscle weakness that is exhibited poststroke is due to a multifactorial etiology involving the central nervous system and skeletal muscle changes. Insulinlike growth factor 1 (IGF-1) and IGF binding protein 3 (IGFBP-3) have been described as biomarkers of neuromuscular performance in many conditions. However, no information about these biomarkers is available for people with chronic hemiparesis. OBJECTIVE: The purpose of this study was to investigate possible factors involved in muscle weakness, such as IGF-1 and IGFBP-3 serum concentrations, muscle volume, and neuromuscular performance of the knee flexors and extensors, in people with chronic hemiparesis poststroke. DESIGN: This was a cross-sectional study. METHODS: A cross-sectional study was performed on 14 individuals poststroke who were paired with healthy controls. Mobility, function, balance, and quality of life were recorded as outcome measures. Knee flexor and extensor muscle volumes and neuromuscular performance were measured using nuclear magnetic resonance imaging, dynamometry, and electromyography. The serum concentrations of IGF-1 and IGFBP-3 were quantified by enzyme-linked immunosorbent assay (ELISA). RESULTS: The hemiparetic group had low serum concentrations of IGF-1 (25%) and IGFBP-3 (40%); reduced muscle volume in the vastus medialis (32%), vastus intermedius (29%), biceps femoris (16%), and semitendinosus and semimembranosus (12%) muscles; reduced peak torque, power, and work of the knee flexors and extensors; and altered agonist and antagonist muscle activation compared with controls. CONCLUSIONS: Low serum concentrations of IGF-1 and IGFBP-3, deficits in neuromuscular performance, selective muscle atrophy, and decreased agonist muscle activation were found in the group with chronic hemiparesis poststroke. Both hemorrhagic and ischemic stroke were considered, and the data reflect a chronic poststroke population with good function.

l-histidine induces state-dependent memory deficit in mice mediated by H(1) receptor.

This study investigated the role of H(1) receptor in the state-dependent memory deficit induced by l-histidine (LH) in mice using Trial 1/2 protocol in the elevated plus-maze (EPM). The test was performed for two consecutive days: Trial 1 (T1) and Trial 2 (T2). Before both trials, mice received a combined injection i.p. of saline+saline (SAL/SAL), 500 mg/kg L-histidine+saline (LH/SAL), 500 mg/kg L-histidine+16 mg/kg chlorpheniramine (LH/CPA) or saline+16 mg/kg chlorpheniramine (SAL/CPA). The trials were performed in the EPM 10 min after the last injection. Each animal was placed in the center of the maze facing the open arm and had five minutes to explore it. On both days, test sessions were videotaped. The behavioral measures were scored from videotape. Data were analyzed based on Analysis of Variance (ANOVA) and the Fisher's LSD test. The data showed no effects on anxiety since there was no difference between the SAL/SAL and the other groups in Trial 1, respectively, open arm entries (OAE), open arm time (OAT) and their percentages (%OAE and %OAT). During Trial 2, OAE, OAT, %OAE and %OAT were reduced in mice treated with SAL/SAL, LH/CPA and SAL/CPA, while the group LH/SAL did not show any difference in these measures. No significant changes were observed in enclosed arm entries (EAE), an EPM index of general exploratory activity. Thus, it can be suggested that LH induces emotional memory deficit and the treatment with chlorpheniramine was able to revert this effect, suggesting this action of LH was mediated by the H(1) receptor.

Effects of treadmill-walking training with additional body load on quality of life in subjects with Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) causes motor and non-motor impairments that affect the subject's quality of life. OBJECTIVE: To assess the effects of treadmill-walking training with additional body load on the quality of life and motor function of subjects with PD. METHODS: Nine subjects with PD, Hoehn and Yahr stages 2-3, not demented and with capability to ambulate independently took part in this study. The training program was divided into three phases (A1-B-A2): treadmill training with additional body load (A1), control condition (conventional physical therapy group; B) and a second period of treadmill training with load (A2). Each phase lasted six weeks. Quality of life and motor function were assessed by the PDQ-39 and the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS), respectively. The evaluations and the training were performed during the on-phase of the medication cycle. RESULTS: There was improvement in the total PDQ-39 score across the training period. The subscores mobility, activities of daily living and cognition subscores significantly improved after the training period. The improvement in the total score was associated with motor and non-motor factors in all of the training phases. The UPDRS motor score also improved, however it did not present any association with the improvement in quality of life. CONCLUSIONS: The results showed that the treadmill-walking training with additional body load allowed an improvement in motor and non-motor aspects related to quality of life and motor function in subjects with PD.

Effects of treadmill-walking training with additional body load on quality of life in subjects with Parkinson's disease / Efeitos do treino da marcha em esteira com aumento da carga corporal sobre a qualidade de vida de sujeitos com doença de Parkinson

BACKGROUND: Parkinson's disease (PD) causes motor and non-motor impairments that affect the subject's quality of life. OBJECTIVE: To assess the effects of treadmill-walking training with additional body load on the quality of life and motor function of subjects with PD. METHODS: Nine subjects with PD, Hoehn and Yahr stages 2-3, not demented and with capability to ambulate independently took part in this study. The training program was divided into three phases (A1-B-A2): treadmill training with additional body load (A1), control condition (conventional physical therapy group; B) and a second period of treadmill training with load (A2). Each phase lasted six weeks. Quality of life and motor function were assessed by the PDQ-39 and the motor score of the Unified Parkinson's Disease Rating Scale (UPDRS), respectively. The evaluations and the training were performed during the on-phase of the medication cycle. RESULTS: There was improvement in the total PDQ-39 score across the training period. The subscores mobility, activities of daily living and cognition subscores significantly improved after the training period. The improvement in the total score was associated with motor and non-motor factors in all of the training phases. The UPDRS motor score also improved, however it did not present any association with the improvement in quality of life. CONCLUSIONS: The results showed that the treadmill-walking training with additional body load allowed an improvement in motor and non-motor aspects related to quality of life and motor function in subjects with PD.

CONTEXTUALIZAÇÃO: A doença de Parkinson (DP) causa prejuízos motores e não-motores que afetam a qualidade de vida dos sujeitos. OBJETIVO: Avaliar os efeitos de um treino de marcha em esteira, com aumento da carga corporal, sobre a qualidade de vida e a função motora de sujeitos com DP. MÉTODOS: Nove sujeitos com DP idiopática, estágio 2 a 3 da escala de Hoehn & Yahr, sem demência e com capacidade de andar independentemente participaram do estudo. O programa de treino foi dividido em três fases (A1-B-A2) de seis semanas cada: treino da marcha em esteira com aumento da carga corporal (A1), condição controle (fisioterapia convencional) (B) e treino da marcha em esteira novamente (A2). A qualidade de vida e a função motora foram avaliadas, respectivamente, pela PDQ-39 e escore motor da UPDRS (Escala Unificada de Avaliação da Doença de Parkinson). As avaliações e os treinos foram realizados na fase on do ciclo da medicação. RESULTADOS: Houve melhora no escore total da PDQ-39 ao longo do período de treino. Os subitens mobilidade, atividades da vida diária e cognição da PDQ-39 melhoraram significativamente após o treino. A melhora no escore total mostrou correlação com fatores motores e não-motores. O escore motor da UPDRS também melhorou, no entanto, não houve correlação com a melhora na qualidade de vida. CONCLUSÃO: Os resultados mostraram que o treino em esteira com aumento de carga corporal permitiu uma melhora de aspectos motores e não-motores relacionados à qualidade de vida e à função motora de sujeitos com DP.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish.

This work investigated the effect of the H1 receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental trials were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (maximum period). Time to find food was analysed in seconds. Animals were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group maintained the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animals and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Chlorpheniramine impairs spatial choice learning in telencephalon-ablated fish

This work investigated the effect of the Hj receptor blockade in the forebrain of ablated Carassius auratus in a simple stimulus-response learning task using a T-maze test with positive reinforcement. The goldfish were submitted to surgery for removal of both telencephalic lobes five days before beginning the experiment. A T-shaped glass aquarium was employed, with two feeders located at the extremities of the long arm. One of the two feeders was blocked. The experimental triáis were performed in nine consecutive days. Each fish was individually placed in the short arm and confined there for thirty seconds, then it was allowed to swim through the aquarium to search for food for ten minutes (máximum period). Time to find food was analysed in seconds. Animáis were injected intraperitoneally with chlorpheniramine (CPA) at 16 mg/kg of body weight or saline after every trial, ten minutes after being placed back in the home aquarium. The results show that all the training latencies of the A-SAL group were higher than the latencies of the S-SAL group. The S-SAL group had decreased latencies from the second trial on, while the S-CPA group showed decreased latencies after the fourth trial. The A-SAL group showed reduced latencies after the fifth trial, but the A-CPA group mainteined the latencies throughout the experiment. This suggests that CPA impairs the consolidation of learning both on telencephalon ablated animáis and in sham-operated ones through its action on mesencephalic structures of the brain and/or on the cerebellum in teleost fish.

Gait training combining partial body-weight support, a treadmill, and functional electrical stimulation: effects on poststroke gait.

BACKGROUND AND PURPOSE: Treadmill training with harness support is a promising, task-oriented approach to restoring locomotor function in people with poststroke hemiparesis. Although the combined use of functional electrical stimulation (FES) and treadmill training with body-weight support (BWS) has been studied before, this combined intervention was compared with the Bobath approach as opposed to BWS alone. The purpose of this study was to evaluate the effects of the combined use of FES and treadmill training with BWS on walking functions and voluntary limb control in people with chronic hemiparesis. SUBJECTS: Eight people who were ambulatory after chronic stroke were evaluated. METHODS: An A(1)-B-A(2) single-case study design was applied. Phases A(1) and A(2) included 3 weeks of gait training on a treadmill with BWS, and phase B included 3 weeks of treadmill training plus FES applied to the peroneal nerve. The Stroke Rehabilitation Assessment of Movement was used to assess motor recovery, and a videography analysis was used to assess gait parameters. RESULTS: An improvement (from 54.9% to 71.0%) in motor function was found during phase B. The spatial and temporal variables cycle duration, stance duration, and cadence as well as cycle length symmetry showed improvements when phase B was compared with phases A(1) and A(2). DISCUSSION AND CONCLUSION: The combined use of FES and treadmill training with BWS led to an improvement in motor recovery and seemed to improve the gait pattern of subjects with hemiparesis, indicating the utility of this combination method during gait rehabilitation. In addition, this single-case series showed that this alternative method of gait training--treadmill training with BWS and FES--may decrease the number of people required to carry out the training.

Involvement of the histaminergic system on appetitive learning and its interaction with haloperidol in goldfish.

This study investigated the actions of the histaminergic system on appetitive learning and memory, and its interaction with the dopaminergic system in goldfish. It consisted of nine sessions, in which fish were tested in a four-arm tank. On day 1, the animals were habituated for 10 min. On day 2, they were placed in one arm and had to find food at the left or the right arm. Time to begin feeding was recorded, and the procedure repeated for more 3 days (training phase). On training day 4, seven groups were injected with saline, seven with haloperidol (2.0 mg/kg) and one with DMSO solution before training and after feeding, three groups received saline, six chlorpheniramine (CPA) (1.0, 4.0 and 8.0 mg/kg), and six l-histidine (LH) (25, 50 and 100 mg/kg). Saline groups were considered as control of CPA and LH treated groups and DMSO as control of haloperidol. A non-injected group was also included. Testing occurred after 24 h. A reversal procedure was conducted 24h after testing and repeated for 3 days. The groups receiving CPA at 1.0 and 8.0 mg/kg and LH at 25, 50 and 100 mg/kg differed between Test and Reversal day 1. Pre-treatment with haloperidol plus 8.0 mg/kg of CPA and 25 and 50 mg/kg of LH reverted the treatment effect. However, in the groups treated with 1.0 mg/kg of CPA and 100 mg/kg of LH, the difference remained. This study confirmed the interaction between the histaminergic and the dopaminergic systems on memory process in goldfish.

Thioperamide delays vestibular compensation in goldfish.

Unilateral lesion of the vestibular system induces posturo-locomotor deficits that are compensated for with time. Drug therapy is currently used to improve the recovery process and to facilitate vestibular compensation. We investigated the effects of thioperamide on functional recovery after unilateral labyrinthectomy in Carassius auratus. Approximately 24h after surgery, the animals were injected intraperitoneally with thioperamide (15 mg/kg) and saline (1.5 ml/kg). The injections were repeated daily for a total of 15 consecutive days. The substances were administered in a volume of 1.5 ml/kg body weight. Another group, which served as a non-lesion control, did not receive unilateral labyrinthectomy or system injections. Animals treated with saline presented a compensatory decrease in body tilt on the 7th day, while the animals treated with thioperamide presented a decrease in body tilt from the 13th day, suggesting a delay in the functional recovery process. These results suggest that an increase in cerebral histamine levels impairs vestibular compensation in goldfish.

Anxiolytic-like effect of chlorpheniramine in inhibitory avoidance in goldfish submitted to telencephalic ablation.

The aim of the present study was to verify the consequences of telencephalic ablation on the learning of inhibitory avoidance and anxiety in goldfish. The animals were submitted to telencephalic ablation or sham operations five days prior to the experimental procedure. 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 and third days, they were injected with saline (SAL), 16 mg/kg Chlorpheniramine (CPA), 40% Propylene glycol (PPG) or 1 mg/kg Diazepam (DZP) twenty minutes 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 the compartments a 45-g weight was dropped. This procedure was performed three times in a row. The groups submitted or not to telencephalic ablation and treated with SAL presented a difference between training sessions; however, the groups treated with CPA, PPG or DZP did not show any differences between them. These results suggest that the treatment with CPA, PPG or DZP impaired the acquisition of inhibitory avoidance conditioning in animals regardless of telecenphalic ablation. In conclusion, telencephalic ablation does not disrupt the animals' capacity to learn the inhibitory avoidance task, and based on the fact that CPA showed similar effects to those of DZP on the animals submitted or not to telencephalic ablation, we suggest that the CPA presents an anxiolytic-like effect mediated by the diencephalon in goldfish.

Involvement of histamine receptors in the acquisition of inhibitory avoidance in Carassius auratus.

This study investigated the involvement of H(1) and H(2) histaminegic receptors on the acquisition of a new task in Carassius auratus by using an inhibitory avoidance paradigm in which the animals had to learn to avoid an aversive stimulus. Before training, the fish received injections of H(2) antagonist zolantidine at a dose of 20 mg/kg, or H(1) antagonist chlorpheniramine at a dose of 4 or 16 mg/kg. Control animals were injected with distilled water. A facilitatory effect of chlorpheniramine was observed at the dose of 16 mg/kg. On the other hand, the administration of 20 mg/kg of zolantidine inhibited acquisition. Place preference conditioning was used to observe the aversive or reinforcing effects of the drugs, which could interfere with the inhibitory avoidance procedure; however, no effects were observed. Thus, it can be suggested that both receptors, H(1) and H(2), are involved in the acquisition of a new task in this species.

Preference of goldfish (Carassius auratus) for dark places

Visando determinar a preferência por ambientes claros ou escuros, peixes dourados (Carassius auratus) foram submetidos a um teste num aquário em que podiam sair de um compartimento central indo seja para um compartimento preto, seja para um compartimento branco. Registrou-se (1) o primeiro compartimento escolhido,(2) a freqüência de entradas em cada compartimento, e (3) o tempo gasto neles. Os resultados mostram que, nas condições experimentais, C. auratus tem preferência significativa pelo escuro, uma característica relevante para o desenvolvimento de um modelo experimental de ansiedade com esta espécie

Effects of Chlorpheniramine and L-histidine on vestibular compensation in goldfish, Carassius auratus.

Histamine is thought to be involved in the recovery of vestibular function after damage to the vestibular receptors of the inner ear. This study evaluated the effects of post-operative treatment using Chlorpheniramine (H1 histamine antagonist) and L-histidine, (a histaminergic precursor), after hemilabyrinthectomy in goldfish. In this lesion model, the unilateral removal of the labyrinth induces a transient postural imbalance in response to light. After the lesion, the animals were injected intraperitoneally, during 12 consecutive days, with Chlorpheniramine, L-histidine and saline. All the substances were administered in a volume of 1 ml/kg body weight. Another group, which served as a non-lesion control, did not receive hemilabyrinthectomy or systemic injections. Chlorpheniramine accelerated the functional recovery when compared with that of the saline group. These data suggest that the inhibition of the histaminergic system facilitates the functional recovery in goldfish.

Neurochemical analysis of brain monoamines after L-histidine and chlorpheniramine administration in goldfish.

This study investigated the effects of chlorpheniramine (CPA) and L-histidine (LH) administration on catecholaminergic levels in goldfish brain using neurochemical analysis. Fifty-eight animals were used. After 20 min of i.p. administration of the drugs or saline the animals were decapitated, and the telencephalon and the diencephalon were dissected. We also measured catecholamines in a non-injected (NI) group. Results showed lower homovanillic acid (HVA) levels after treatment with 100 mg/kg of LH when compared to saline and 5-hydroxyindoleacetic acid levels were lower in the saline group when compared to the NI group. In the diencephalon the NI group and animals treated with CPA at 4.0 and 8.0 mg/kg had lower HVA levels. Results suggest that LH had an inhibitory effect on dopaminergic activity and an anxiolytic-like effect for CPA results is suggested.