RESUMO
The possible role of histamine sensitive sites in hippocampus and the nucleus accumbens on memory and exploratory motivation was studied. As a model of memory, the learning of an active avoidance response to an ultrasonic tone anticipating an electric shock was used. As a model of motivation, an elevated asymmetric plus-maze with arms differing in the presence or absence of walls (APM) was used. All rats were implanted with microinjection cannulae into the ventral, dorsal hippocampus or the nucleus accumbens. Animals were stimulated with histamine, with or without histamine receptor antagonists 5 min before training trials in memory or exploration tests in the APM. Results show that histamine in ventral hippocampus inhibits evocation, impairing the efficiency of learning (37.5+/-6.5 vs. 75+/-5.2% of accumulated conditioning responses; histamine vs. saline, P<0.01). This inhibitory action was blocked by pyrilamine (H(1)-histamine receptor antagonist) but not by ranitidine (H(2)-histamine receptor antagonist). In dorsal hippocampus no significant inhibitory effect due to histamine stimulation was observed. In the APM, histamine in the nucleus accumbens increased exploration of the fear-inducing arms (45+/-12 vs. 16+/-8 counts per 5 min; histamine vs. saline, P<0.01) and also increased the emotionality index. These effects were blocked by both histamine receptor antagonists. In conclusion, data suggest a modulating role for histamine in learning and motivation/emotionality processes in the rat brain.
Assuntos
Histamina/fisiologia , Aprendizagem/fisiologia , Sistema Límbico/fisiologia , Memória/fisiologia , Motivação , Animais , Aprendizagem da Esquiva/fisiologia , Mapeamento Encefálico , Comportamento Exploratório/fisiologia , Medo/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Núcleo Accumbens/fisiologia , Ratos , Receptores Histamínicos H1/fisiologia , Receptores Histamínicos H2/fisiologiaRESUMO
The possible role of glutamic acid locally applied into the nucleus accumbens on exploratory behaviours measured in 'conflictive' and 'non-conflictive' environments was studied in adult male rats. As a model of conflictive environment, the elevated asymmetric-plus maze (APM) was used. As a model of a non-conflictive environment, a modified holeboard enriched with an object (OVM) was used. In order to characterize the possible glutamic acid receptors involved, the following antagonists were also used: AP3 (antagonist of the metabotropic glutamic acid receptor), AP7 (antagonist of NMDA glutamic acid receptor, and CNQX (antagonists of kainate/AMPA glutamic acid receptor). Results showed that injection of glutamic acid into the nucleus accumbens induced in the APM a decrease of exploration and an increase of the permanency score (non-exploratory behaviours) of the 'High and Low wall' arm. However, in the 'Two High Walls' arm, glutamic acid decreased permanency. In the OVM, no major changes in the motor activity were observed with glutamic acid. Nevertheless, the vertical activity (an index of rearing) and head-dipping were inhibited by the amino-acid treatment. In the APM, the decrease of exploration induced by glutamic acid was blocked by all three receptor antagonists. In the non-exploratory behaviours, the facilitatory effect observed in the 'High and Low walls' arm was blocked only by AP7 and CNQX. The inhibitory action of glutamic acid on the permanency score in the 'Two High Walls' arm was not blocked by the receptors antagonists. In the OVM, AP7 and CNQX were effective in blocking the inhibition of glutamic acid on the vertical activity, but in head-dipping, only AP3 and CNQX were able to block the effect of the amino acid on this behaviour. In conclusion, the present results are compatible with the concept that glutamatergic input fibres to the nucleus accumbens modulate the expression of exploratory behaviour induced by novelty in conflictive and non-conflictive conditions.
Assuntos
Nível de Alerta/fisiologia , Conflito Psicológico , Ácido Glutâmico/fisiologia , Núcleo Accumbens/fisiologia , Receptores de Glutamato/fisiologia , Meio Social , Animais , Mapeamento Encefálico , Comportamento Exploratório/fisiologia , Masculino , Aprendizagem em Labirinto/fisiologia , Motivação , Fibras Nervosas/fisiologia , Inibição Neural/fisiologia , Ratos , Receptores de AMPA/fisiologia , Receptores de Glutamato Metabotrópico/fisiologia , Receptores de N-Metil-D-Aspartato/fisiologiaRESUMO
The possible functional regional distribution of the histamine sensitive sites controlling the behavioral performance of learning of an active avoidance response in the hippocampal structure was studied. Adult male rats were stereotaxically implanted with microinjection cannula into three different regions of the hippocampus: the ventral, the dorsal posterior and the dorsal anterior hippocampus. Different groups of rats were microinjected into these subregions with either saline, 9, 45 or 90 nmol of histamine. Five min later all groups were subjected to learning of a conditioned response to an ultrasonic tone warning an electric shock to the feet of the animals. Three sessions of 8 trials were necessary in order to control animals learn the task. Results show that histamine microinjections into the ventral hippocampus were able to significantly inhibit the natural decrease of the latency to escape during trials, impairing the efficiency of learning. Histamine administration into the dorsal posterior hippocampus was slightly effective in prolonging latency and impairing learning, while injections into the dorsal anterior region of the hippocampus had no effect. Results give a further support to the idea that histamine sensitive neurons in the ventral hippocampus are modulating the memory and learning mechanisms in the rat. In addition, evidence has been found suggesting a regional distribution of histamine sensitive neurons controlling learning of avoidance responses along the septo-temporal axis of the rat hippocampus.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Hipocampo/metabolismo , Receptores Histamínicos/metabolismo , Animais , Condicionamento Psicológico/fisiologia , Reação de Fuga/efeitos dos fármacos , Reação de Fuga/fisiologia , Hipocampo/anatomia & histologia , Hipocampo/fisiologia , Histamina/administração & dosagem , Histamina/metabolismo , Histamina/fisiologia , Masculino , Microinjeções , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Tempo de Reação/fisiologia , Receptores Histamínicos/fisiologiaRESUMO
The role of ventral hippocampus glutamate receptors on learning mechanisms and memory was studied in the rat. Adult male rats were unilaterally implanted in the ventral hippocampus with microinjection cannulas. The general experimental procedure used was the chemical stimulation of hippocampal neurons with glutamic acid alone or in combination with glutamate receptor antagonists during learning of an active avoidance response. The one-way active response consisted in avoiding an electric shock applied to the feet while an ultrasonic tone of 40 KHz was on. Two series of experiments were performed. In Experiment 1, the possible effect of glutamate on the evocation of the learned avoidance response was studied. In Experiment 2, the possible effect of glutamate on the acquisition of the avoidance response was analyzed. Experiment 1 showed that glutamate in the range 1-10 nmol did not interfere with the recall of the avoidance response, suggesting that glutamate has no effect on the hippocampal evocation processes. Experiment 2 showed that glutamic acid inhibits the acquisition process, increasing the latency time of escape and deteriorating the learning efficiency. This effect was antagonized by AP7, the NMDA-glutamate receptor antagonist, and increased by AP3, the metabotropic glutamate receptor antagonist. Present data suggest that metabotropic glutamate receptors facilitate and NMDA-glutamate receptors inhibit the learning hippocampal mechanisms in the rat.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Antagonistas de Aminoácidos Excitatórios/farmacologia , Hipocampo/efeitos dos fármacos , Tempo de Reação/efeitos dos fármacos , Receptores de Glutamato/efeitos dos fármacos , Glutamato de Sódio/farmacologia , Animais , Hipocampo/química , Masculino , Memória/efeitos dos fármacos , Microinjeções , Ratos , Receptores de Glutamato/fisiologiaRESUMO
The possible role of histamine locally applied into the nucleus accumbens on exploratory behaviours measured in 'conflictive' and 'non-conflictive' environments was studied in adult male rats. It was assumed that in conflictive environments the brain mechanisms involved in processing incentive environmental clues (novelty) were interacting with mechanisms involved in the processing of fearful or 'anxiogenic' environmental clues. As a model of conflictive environment, the elevated asymmetric-plus maze (APM) was used. As a model of a non-conflictive environment, a modified holebroad enriched with an object (OVM) was used. The exploration score in any of the arms of the APM was considered an approximate index of exploratory motivation. The permanency score (non-exploratory behaviours) was considered an inverse approximate index of emotionality. Other variables such as the frequency of entries into any arm, the latency time and central activity were also measured. In the OVM, the general motor activity and head-dipping, vertical rearing and focalized exploration were measured. Results show that histamine in the APM had a dual effect. On the one hand, an increase of exploration was observed in those arms considered more 'anxiogenic'. On the other hand, a decrease in exploration occurred in one of the arms considered less 'anxiogenic'. No changes of permanency was observed in the 'anxiogenic' arms, and a decrease of permanency took place in the arms considered less 'anxiogenic'. In the OVM, histamine did not change the overall motor activity, but head-dipping was inhibited by the imidazolamine treatment. Histamine effects on exploration parameters were counteracted by pre-treatment with H1- and H2-histamine antagonists. Nevertheless, some behaviours were not blocked by the histamine receptor antagonists. The present results give support to the role of the nucleus accumbens in the exploratory motivation mechanisms and suggest that histamine might be an endogenous regulator.
Assuntos
Comportamento Exploratório/efeitos dos fármacos , Antagonistas dos Receptores Histamínicos/farmacologia , Histamina/farmacologia , Núcleo Accumbens/efeitos dos fármacos , Animais , Nível de Alerta/efeitos dos fármacos , Mapeamento Encefálico , Medo/efeitos dos fármacos , Injeções , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Motivação , Pirilamina/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Sprague-Dawley , Tempo de Reação/efeitos dos fármacos , Meio SocialRESUMO
When rats are exposed to unknown environments where novelty and fear-inducing characteristics are present (conflictive environments), some specific behaviors are induced and exploration is apparently modulated by fear. In our laboratory, a new type of plus-maze was designed as a model of conflictive exploration. The maze is composed of four arms with different geometrical characteristics, differing from each other by the presence or absence of walls. The degree of asymmetry was as follows: NW, no wall arm; SW, a single high wall present; HL, a low and a high wall present, and HH, two high walls present. The four arms were arranged at 90 degrees angles and the apparatus was called the elevated asymmetric plus-maze (APM). The purpose of the present study was to assess the behavioral profile of rats exposed for a single time to the APM with or without treatment with benzodiazepine. Increasing doses of diazepam were injected intraperitoneally in several groups of male, 90-day-old Holtzman rats. Distilled water was injected in control animals. Thirty minutes after treatment all rats were exposed singly to a 5-min test in the APM. Diazepam induced a biphasic modification of exploration in the NW and SW arms. The increase in the exploration score was evident at low doses of diazepam (0.25-1.0 mg/kg body weight) and the decrease in exploration was found with the higher doses of diazepam (2.0-3.0 mg/kg body weight). Non-exploratory behaviors (permanency) were not affected by benzodiazepine treatment. In the HL arm, exploration was not modified but permanency was increased in a dose-dependent manner. In the HH arm, exploration and permanency were not affected. Results are compatible with the idea that exploration-processing mechanisms in conflictive environments are modulated by fear-processing mechanisms of the brain.
Assuntos
Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
When rats are exposed to unknown environments where novelty and fear-inducing characteristics are present (conflictive environments), some specific behaviors are induced and exploration is apparently modulated by fear. In our laboratory, a new type of plus-maze was designed as a model of conflictive exploration. The maze is composed of four arms with different geometrical characteristics, differing from each other by the presence or absence of walls. The degree of asymmetry was as follows: NW, no wall arm; SW, a single high wall present; HL, a low and a high wall present, and HH, two high walls present. The four arms were arranged at 90o angles and the apparatus was called the elevated asymmetric plus-maze (APM). The purpose of the present study was to assess the behavioral profile of rats exposed for a single time to the APM with or without treatment with benzodiazepine. Increasing doses of diazepam were injected intraperitoneally in several groups of male, 90-day-old Holtzman rats. Distilled water was injected in control animals. Thirty minutes after treatment all rats were exposed singly to a 5-min test in the APM. Diazepam induced a biphasic modification of exploration in the NW and SW arms. The increase in the exploration score was evident at low doses of diazepam (0.25-1.0 mg/kg body weight) and the decrease in exploration was found with the higher doses of diazepam (2.0-3.0 mg/kg body weight). Non-exploratory behaviors (permanency) were not affected by benzodiazepine treatment. In the HL arm, exploration was not modified but permanency was increased in a dose-dependent manner. In the HH arm, exploration and permanency were not affected. Results are compatible with the idea that exploration-processing mechanisms in conflictive environments are modulated by fear-processing mechanisms of the brain
Assuntos
Ratos , Animais , Masculino , Ansiolíticos/farmacologia , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Comportamento Exploratório/efeitos dos fármacos , Aprendizagem em Labirinto/efeitos dos fármacos , Ratos Sprague-DawleyRESUMO
The possible role of histamine receptors in the hippocampal formation on the exploratory motivation and emotionality of the rat was studied. An elevated asymmetric plus-maze composed of 4 different arms (no walls, single high wall, high and low walls and two high walls) arranged at 90 degrees angles was used. The exploration score, considered to be an index of exploratory motivation, and the permanency score, considered to be an index of emotionality (anxiety), were determined. Histamine was administered locally into the ventral hippocampus at three different doses (9,45 and 90 nmol). Another group of rats was also microinjected with 45 nmol of pyrilamine (a histamine H1 receptor antagonist) or ranitidine (a histamine H2 receptor antagonist) in addition to 9 nmol of histamine in order to identify the possible type of histamine receptor involved. Histamine administration significantly inhibited the exploration score and increased the permanency score at the doses of 9 and 45 nmol in two of four arms. These effects were completely blocked by the administration of eitheer histamine receptor antagonist. The present results suggest that in the hippocampal formation histamine inhibits exploratory motivation and decreases emotionality by activating both types of histamine receptors. Also, the elvated asymmetric plus-maze appears to be a suitable technique to quantify exploration and possibly "anxiety".
Assuntos
Ratos , Animais , Masculino , Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Histamina/farmacologia , Aprendizagem em Labirinto/efeitos dos fármacos , Pirilamina/farmacologia , Ranitidina/farmacologia , Receptores Histamínicos/fisiologia , Ratos Sprague-DawleyRESUMO
The possible role of histamine receptors in the hippocampal formation on the exploratory motivation and emotionality of the rat was studied. An elevated asymmetric plus-maze composed of 4 different arms (no walls, single high wall, high and low walls and two high walls) arranged at 90 degrees angles was used. The exploration score, considered to be an index of exploratory motivation, and the permanency score, considered to be an index of emotionality (anxiety), were determined. Histamine was administered locally into the ventral hippocampus at three different doses (9, 45 and 90 nmol). Another group of rats was also microinjected with 45 nmol of pyrilamine (a histamine H1 receptor antagonist) or ranitidine (a histamine H2 receptor antagonist) in addition to 9 nmol of histamine in order to identify the possible type of histamine receptor involved. Histamine administration significantly inhibited the exploration score and increased the permanency score at the doses of 9 and 45 nmol in two of four arms. These effects were completely blocked by the administration of either histamine receptor antagonist. The present results suggest that in the hippocampal formation histamine inhibits exploratory motivation and decreases emotionality by activating both types of histamine receptors. Also, the elevated asymmetric plus-maze appears to be a suitable technique to quantify exploration and possibly "anxiety".
Assuntos
Comportamento Exploratório/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/fisiologia , Aprendizagem em Labirinto/efeitos dos fármacos , Receptores Histamínicos/fisiologia , Animais , Histamina/farmacologia , Masculino , Pirilamina/farmacologia , Ranitidina/farmacologia , Ratos , Ratos Sprague-DawleyRESUMO
In this paper it was studied the role of histamine and histamine receptors in the hippocampus of rats on an active avoidance response induced by an ultrasonic tone. The animals had to learn to walk through a swinging door into a safe compartment only after the conditioning ultrasonic tone was on in order to avoid an electric shock to their feet. Trained animals were implanted in the ventral hippocampus with microinjection cannulae and injected twice with 1 microliter of saline solution containing pyrilamine (PYR, H1-HA antagonist), ranitidine (RAN, H2-HA antagonist) or histamine. The histamine antagonists were applied in a dose of 65.5 nmol each while histamine was administered in a dose of 45 nmol. The two variables measured were the time in sec the rats take to present the conditioned avoidance response and the accumulated percentage of conditioned avoidance response (CAR). Results showed that histamine administration significantly increased the latency time to escape and decreased the % CAR. These effects were not blocked by the administration of RAN. However, administration of PYR completely counteracted the HA effects. Present findings confirm our previous findings about the inhibitory effect of histamine on the hippocampal retrieval mechanisms and give further support to the hypothesis that HA acts on the memory processes in the hippocampal formation, by activation of H1-histamine receptors.