RESUMO
Microinjections of serotonin and glutamic acid into the globus pallidus in conditions of free selection between a light and a dark chamber showed these substances to have antiaversive activity in rats in the "threatening situation" test but not in the "illuminated area" test. Local administration of dopamine and GABA into this basal ganglia formation had no effect on the mechanisms of voluntary movement but countered anxiety states in both behavioral models. These results provide evidence that the neurotransmitter systems of the dorsal pallidum have different degrees of involvement in the operative control of behavior when the modality of the aversive stimulus changes.
Assuntos
Aminoácidos/farmacologia , Ansiedade/prevenção & controle , Ansiedade/psicologia , Monoaminas Biogênicas/farmacologia , Globo Pálido/fisiologia , Aminoácidos/agonistas , Aminoácidos/antagonistas & inibidores , Animais , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Condicionamento Operante/efeitos dos fármacos , Globo Pálido/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Ácido Glutâmico/farmacologia , Masculino , Microinjeções , Motivação , Atividade Motora/efeitos dos fármacos , Ratos , Reforço Psicológico , Serotonina/farmacologia , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/farmacologiaRESUMO
Microinjections of serotonin and glutamine acid into the globus pallidus reveal antiaversive properties of these subsrances in the test with avoiding "threatening situation" but not "illuminated site" test under conditions of rats' free choice between light and dark sites. Dopamine and GABA injected locally into this formation of basal ganglia do not affect the mechanisms of voluntary movement, but counteract the conditions of anxiety in both models of behavior. The results testify to unequal involvement of neurotransmitter systems of the dorsal pallidum into operative regulation of behavior with changes of aversive stimulus modality.
Assuntos
Ansiedade/fisiopatologia , Monoaminas Biogênicas/fisiologia , Globo Pálido/fisiopatologia , Ácido Glutâmico/fisiologia , Aminoácidos/farmacologia , Aminoácidos/fisiologia , Animais , Ansiedade/etiologia , Ansiedade/psicologia , Comportamento Animal , Monoaminas Biogênicas/farmacologia , Reação de Fuga/efeitos dos fármacos , Globo Pálido/efeitos dos fármacos , Globo Pálido/fisiologia , Ácido Glutâmico/farmacologia , Masculino , Ratos , Serotonina/farmacologiaRESUMO
In conditions in which rats had a free choice between dark and light chambers, microinjections of glutamic acid, serotonin, and campiron into the globus pallidus showed that these agents have antiaversive properties in a threatening situation test but not in an illuminated area test. Dopamine, apomorphine, GABA, chlordiazepoxide, phenibut, and indoter injected locally into this formation of the basal ganglia had no effect on the mechanisms of voluntary movement but counteracted anxiety states in both behavioral models. These results provide evidence that the monoaminergic and aminoacidergic systems of the dorsal pallidum have different functional roles in the operative regulation of behavior for aversive stimuli of different modalities. Prior intraperitoneal administration of functional antagonists of these synaptotropic substances and subsequent microinjection of transmitter monoamines and amino acids and their agonists into the globus pallidus demonstrated the selective involvement of the neurotransmitter systems of the dorsal pallidum in the antiaversive effects of anxiosedative and anxioselective substances.
Assuntos
Ansiolíticos/administração & dosagem , Ansiedade/metabolismo , Aprendizagem da Esquiva/fisiologia , Comportamento Animal/fisiologia , Globo Pálido/metabolismo , Neurotransmissores/administração & dosagem , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Comportamento Animal/efeitos dos fármacos , Aminas Biogênicas/administração & dosagem , Clordiazepóxido/administração & dosagem , Medo/fisiologia , Globo Pálido/efeitos dos fármacos , Ácido Glutâmico/administração & dosagem , Harmina/administração & dosagem , Harmina/análogos & derivados , Masculino , Microinjeções , Piperazinas/administração & dosagem , Pirimidinas/administração & dosagem , Ratos , Estatísticas não Paramétricas , Ácido gama-Aminobutírico/administração & dosagem , Ácido gama-Aminobutírico/análogos & derivadosRESUMO
Preliminary intraperitoneal injections of some combinations of adreno- and dopaminomimetics, monoamines, and mediator amino acids (as well as of their agonists and antagonists) followed by microinjections of the same combinations into the ventral pallidum reveal differences in the functional significance of the neurochemical profile of this paleostriatum formation in realization of the anxiety states of different genesis, as manifested in the "illuminated site avoidance" and the "threatening situation" tests in rats. The pharmacological analysis based on the local injection of anxiosedative and anxioselective agents into the ventral paleostriatum showed that the antiaversive action of campirone is revealed under the conditions of dominating fear motivation, while that analogous action of chlordiazepoxide, phenibut and indoter is revealed under negative stressful zoosocial impacts and is realized by serotonin- and GABA-ergic (rather than by cathecholamine- and glutaminergic) aversive systems of the ventral pallidum.
Assuntos
Ansiolíticos , Ansiedade/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Globo Pálido/efeitos dos fármacos , Animais , Ansiolíticos/administração & dosagem , Ansiolíticos/farmacologia , Ansiolíticos/uso terapêutico , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/efeitos dos fármacos , Reação de Fuga/efeitos dos fármacos , Globo Pálido/química , Globo Pálido/fisiologia , Masculino , Atividade Motora/efeitos dos fármacos , RatosRESUMO
In experiments on rats using an "illuminated area" avoidance test and a "threatening situation" avoidance test, preliminary i.p. administration and subsequent microinjection into the ventromedial hypothalamus of various combinations of monoamines, transmitter amino acids, and their agonists and antagonists demonstrated differences in the functional importance of the neurochemical profile of this limbic formation in mediating anxiety states of different origins. The neurochemical analysis with local intrahypothalamic administration of anxiosedative and anxioselective substances showed that the antiaversive actions of Campirone are obtained only in conditions in which the dominant motivation is fear, while chlordiazepoxide, Phenibut, and Indoter are also active in anxiety induced by negatively stressful zoosocial influences; these actions are mediated respectively by serotoninergic and GABAergic types of synaptic switching in the ventromedial hypothalamus.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Química Encefálica , Núcleo Hipotalâmico Ventromedial/metabolismo , Ácido gama-Aminobutírico/análogos & derivados , Agonistas alfa-Adrenérgicos , Antagonistas Adrenérgicos alfa , Antagonistas Adrenérgicos beta , Animais , Anticonvulsivantes , Ansiedade/metabolismo , Apomorfina/farmacologia , Aprendizagem da Esquiva/efeitos dos fármacos , Biguanidas/farmacologia , Clordiazepóxido/farmacologia , Clonidina/farmacologia , Modelos Animais de Doenças , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Droperidol/farmacologia , Interações Medicamentosas , GABAérgicos/farmacologia , Antagonistas GABAérgicos , Moduladores GABAérgicos , Ácido Glutâmico/farmacologia , Masculino , Memantina/farmacologia , Mefenitoína/farmacologia , Microinjeções/métodos , Pentilenotetrazol/farmacologia , Fentolamina , Picrotoxina/farmacologia , Piperazinas/farmacologia , Propranolol/farmacologia , Pirimidinas/farmacologia , Ratos , Serotonina/farmacologia , Sulpirida/farmacologia , Núcleo Hipotalâmico Ventromedial/química , Ioimbina/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
Experiments using the "illuminated site" and "threatening situation" avoidance tests on rats after preliminary intraperitoneal injection of monoamines, mediator amino acids, and their agonists and antagonists, followed by microinjection of the same combinations into the posterior hypothalamus revealed functional ambiguity in the neurochemical profile of this limbic brain formation in realization of the anxiety states of various genesis. Pharmacological analysis was performed after preliminary injection of various anxiosedative and anxioselective agents into the posterior hypothalamus. It was found that the antiaversive action of chloridiazepoxide, fenibut, and indoter is manifested only under conditions of dominating fear motivation and is mediated by a GABAergic mechanism in the posterior hypothalamus. The anxiolytic effect of campiron is manifested only under negative-stressor zoosocial impact conditions and is mediated by the serotoninergic profile of synaptic switching in this limbic brain formation.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/fisiopatologia , Reação de Fuga/fisiologia , Hipotálamo Posterior/fisiologia , Serotonina/fisiologia , Ácido gama-Aminobutírico/fisiologia , Animais , Reação de Fuga/efeitos dos fármacos , Hipotálamo Posterior/efeitos dos fármacos , Masculino , RatosRESUMO
The experiments using "illuminated site" and "threatening situation" avoidance tests on rats microinjected with GABA, glutamic acid, monoamines and their agonists and antagonists, as well as anxiosedative and anxioselective agents into the anterior hypothalamus revealed functional ambiguity in the neurochemical profile of this limbic brain formation in the anxiety states of various aversive genesis. Preliminary intraperitoneal injection of the monoamine and GABA antagonists, followed by the local administration of the antianxiety drugs studied, showed that the antiaversive action of chlordiazepoxide, fenibut, and indoter is manifested in both anxiety models via a GABAergic mechanism in the anterior hypothalamus. The anxiolytic effect of campiron is manifested only under negative-stressor zoosocial conditions and is mediated by the serotoninergic systems of this limbic brain formation.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Aprendizagem da Esquiva/efeitos dos fármacos , Monoaminas Biogênicas , Ácido Glutâmico , Hipnóticos e Sedativos/farmacologia , Hipotálamo Anterior/efeitos dos fármacos , Ácido gama-Aminobutírico , Animais , Ansiedade/psicologia , Monoaminas Biogênicas/antagonistas & inibidores , Monoaminas Biogênicas/farmacologia , Clordiazepóxido/farmacologia , Modelos Animais de Doenças , Agonistas de Aminoácidos Excitatórios/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Agonistas GABAérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Ácido Glutâmico/farmacologia , Injeções Intraperitoneais , Masculino , Microinjeções , Piperazinas/farmacologia , Pirimidinas/farmacologia , Ratos , Ácido gama-Aminobutírico/análogos & derivados , Ácido gama-Aminobutírico/farmacologiaRESUMO
Microinjections of glutamic acid, serotonin, and sulpiride in the ventromedial hypothalamus reduced anxiety in an illuminated platform avoidance task in rats, while dopamine, apomorphine, picrotoxin, and memantine increased it. Similar injections of phenylephrine and yohimbine reduced anxiety in threatening situation task only, while GABA reduced it in both tasks. It is suggested that various emotional and stress phenotypes are realized through functionally different neurochemical mechanisms of ventromedial hypothalamus.
Assuntos
Ansiedade/fisiopatologia , Hipotálamo Médio/metabolismo , Neurotransmissores/farmacologia , Adrenérgicos/farmacologia , Animais , Apomorfina/farmacologia , Aprendizagem da Esquiva/fisiologia , Modelos Animais de Doenças , Dopamina/farmacologia , Dopaminérgicos/farmacologia , Antagonistas GABAérgicos/farmacologia , Ácido Glutâmico/farmacologia , Hipotálamo Médio/química , Hipotálamo Médio/efeitos dos fármacos , Masculino , Memantina/farmacologia , Microinjeções , Fenilefrina/farmacologia , Picrotoxina/farmacologia , Ratos , Serotonina/farmacologia , Sulpirida/farmacologia , Ioimbina/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
Neurochemical analysis using anxiosedative and anxioselective agents injected into the hypothalamus revealed that antiaversive action of camprione is only realised under conditions of domineering fear motivation whereas that of chlordiazepoxide, phenibut, indoter may also be realised under conditions of negative stressful zoo-social impacts mediated by serotonin.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/metabolismo , Harmina/análogos & derivados , Hipotálamo Médio/metabolismo , Ácido gama-Aminobutírico/análogos & derivados , Antagonistas Adrenérgicos alfa/farmacologia , Aminoácidos/agonistas , Aminoácidos/antagonistas & inibidores , Aminoácidos/farmacologia , Animais , Ansiedade/etiologia , Aprendizagem da Esquiva/efeitos dos fármacos , Monoaminas Biogênicas/agonistas , Monoaminas Biogênicas/antagonistas & inibidores , Monoaminas Biogênicas/farmacologia , Clordiazepóxido/farmacologia , Antagonistas dos Receptores de Dopamina D2 , Antagonistas GABAérgicos/farmacologia , Harmina/farmacologia , Microinjeções , Piperazinas/farmacologia , Pirimidinas/farmacologia , Ratos , Receptores de GABA-A/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Serotoninérgicos/farmacologia , Ácido gama-Aminobutírico/farmacologiaRESUMO
In the experiments on rats in avoidance response to "eliminated area" and "threatening situation" it is found that the microinjection of monoamines and amino-acids of mediator action, adreno- and dophaminemimetics, their antagonists, and blocker of GABAA receptors picrotoxine into dorsal and ventral sections of caudate nucleus elucidates different functional value and neurochemical special features of examined neostriatum specimens in realization of anxiety states of different origin. Local injection of chlordiazepoxide, phenibutum, indoterum, campirone and campironine into aforementioned sections of the caudate nucleus reduces the state of anxiety in "eliminated area" and/or "threatening situation" response tests thus revealing the similarity with well-known effects of GABA and serotonin and substantial difference in the effects of catecholamines and glutamine acid. It is found that anti-anxious effect of benzodiazepine and nonbenzodiazepine anxiolytics can be mediated through participation of neuron matrices of dorsal and ventral sections of the caudate nucleus having functionally ambiguous neurochemical profile.
Assuntos
Ansiolíticos/uso terapêutico , Ansiedade/tratamento farmacológico , Núcleo Caudado/efeitos dos fármacos , Modelos Animais de Doenças , Animais , Ansiolíticos/farmacologia , Ansiedade/metabolismo , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Benzodiazepinas , Núcleo Caudado/metabolismo , Relação Dose-Resposta a Droga , Masculino , RatosRESUMO
Administration of anxio-sedative drugs into the rat caudate nucleus revealed that antiaversive effects of chlordiazepide, phemibut, and indoter only occur under dominating fear motivation, whereas antiaversive effects of campirone and campironine occur under the influence of negative or stressful zoo-social actions and are realised via the GABA- and serotoninergic type of synaptic switching in the dorsal part of the caudate nucleus.
Assuntos
Aminoácidos/metabolismo , Ansiedade/tratamento farmacológico , Monoaminas Biogênicas/metabolismo , Núcleo Caudado/metabolismo , Tranquilizantes/farmacologia , Aminoácidos/farmacologia , Animais , Ansiedade/metabolismo , Monoaminas Biogênicas/farmacologia , Masculino , Microinjeções , Neostriado , Ratos , Serotonina/fisiologia , Ácido gama-Aminobutírico/fisiologiaRESUMO
In experiments on rats with tests for avoidance of an "illuminated area" and a "threatening situation", microinjection into the septal nucleus accumbens of monoamines and GABA, adreno- and dopaminomimetics, and their antagonists demonstrated a different neurochemical profile of this brain structure in anxiety states of different genesis. Local injections of chlordiazepoxide, pnenibut, indoter, campiron, and campironin into the nucleus weakened the alarm in the test for avoidance of an "illuminated area" and/or a "threatening situation", showing a similarity to the effects of GABA and serotonin but not to those of mesaton (phenylephrine hydrochloride) and dopamine. It is concluded that the antialarm effect of benzodiazepine and nonbenzodiazepine anxiolytics may be mediated by switching into action of neuron matrices of the accumbens nucleus with a different neurochemical profile responsible for the operative control of behavior in changed modality of the aversive stimulus.
Assuntos
Ansiolíticos/farmacologia , Ansiedade/tratamento farmacológico , Modelos Animais de Doenças , Núcleo Accumbens/efeitos dos fármacos , Animais , Ansiolíticos/administração & dosagem , Ansiedade/fisiopatologia , Benzodiazepinas , Avaliação Pré-Clínica de Medicamentos , Masculino , Microinjeções , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Núcleo Accumbens/fisiopatologia , RatosRESUMO
Chlordiazepoxid, phenibut, indoter, campiron, campironin, when administered into the amygdala, improve the anxiety condition of rats in avoidance tests and resemble by their effects dophamine, GABA, or serotonin. Observed differences in the anxiolytic effects between anxiosedative and anxioselective agents seem to be due to an unequal contribution of the monoamin- and aminoacidotergic transmitters into the mechanisms of heteromodal aversive anxiety genesis in the basolateral area of the amygdalar complex.
Assuntos
Tonsila do Cerebelo/metabolismo , Tonsila do Cerebelo/fisiologia , Ansiedade/metabolismo , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Condicionamento Clássico , Eletrochoque , Masculino , Microinjeções , Psicotrópicos/farmacologia , RatosAssuntos
Ansiedade/tratamento farmacológico , Aprendizagem da Esquiva/efeitos dos fármacos , Modelos Animais de Doenças , Núcleos Septais/efeitos dos fármacos , Tranquilizantes/uso terapêutico , Animais , Ansiedade/etiologia , Ansiedade/fisiopatologia , Aprendizagem da Esquiva/fisiologia , Condicionamento Clássico/efeitos dos fármacos , Condicionamento Clássico/fisiologia , Avaliação Pré-Clínica de Medicamentos , Masculino , Microinjeções , Ratos , Núcleos Septais/fisiopatologiaRESUMO
Chemical stimulation of the central nucleus of the amygdalar complex was carried out in rats during performance of tests of avoidance of "lighted square" and "threatening situation". Microinjections of monoamines, GABA, glutamate, some of their receptor agonists and antagonists revealed neurochemical heterogeneity of the structure and functional ambiguity of neurotransmitter systems in genesis of anxiety of different aversive modes. Chlordiazepoxid, phenibut, indoter, campiron, campironin decrease anxiety in the tests of avoidance of "lighted square" and "threatening situation", their effects being similar to those of dopamine, GABA, or serotonin. A conclusion is made that distinctions in spectra of anxiosedative and anxioselective drugs under study may be caused by unequal contribution of monoamine and amino acid transmitter mechanisms of the central region of the amygdalar complex in genesis of heteromodal aversive anxiety.
Assuntos
Tonsila do Cerebelo/efeitos dos fármacos , Ansiolíticos/farmacologia , Ansiedade/fisiopatologia , Modelos Animais de Doenças , Tonsila do Cerebelo/metabolismo , Animais , Ansiolíticos/administração & dosagem , Ansiedade/etiologia , Aprendizagem da Esquiva/efeitos dos fármacos , Aprendizagem da Esquiva/fisiologia , Masculino , Microinjeções , RatosRESUMO
In tests of "illuminated area" and the "threatening situation" avoidance by rats, apomorphine and phenamine, administered intraperitoneally, attenuate the state of alarm. A similar effect is observed when sulpiride, a selective blocker of D2-receptors of dopamine, and of picrotoxin, a GABA antagonist, are administered. Sulpiride effectively counteracts the anxiolytic effects of all of the dopaminomimetics investigated and of picrotoxin. Haloperidol, a nonselective blocker of the D1- and D2-receptors of dopamine removes the anxiolytic effect of apomorphine, phenamine, and picrotoxin. The microinjection into the ventral region of the midbrain tegmentum of dopamine, or of sulpiride into the nucleus accumbens of the septum, attenuates the state of alarm formed by aversive influences of various biological modalities. By contrast, sulpiride, introduced locally into the tegmentum, or chemical stimulation of the nucleus accumbens of the septum by dopamine, intensifies the state of alarm in the "illuminated area" avoidance test. The participation of dopaminergic mechanisms of the mesolimbic system of the brain in anxiety of various aversive causations is discussed.
Assuntos
Ansiedade/fisiopatologia , Encéfalo/fisiopatologia , Dopamina/fisiologia , Animais , Química Encefálica/efeitos dos fármacos , Dopamina/farmacologia , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacologia , Antagonistas GABAérgicos/farmacologia , Masculino , Microinjeções , Atividade Motora/efeitos dos fármacos , Relaxantes Musculares Centrais/farmacologia , Ratos , Receptores de Dopamina D1/agonistas , Receptores de Dopamina D1/antagonistas & inibidoresRESUMO
Dopamine and glutamine acid microinjection in the locus coeruleus of rats does not influence the alarm state in the test of "Threatening situation" avoidance, but weakens the state of alarm in the test of "illuminated site" avoidance. The local injection of GABA and noradrenaline mesatone effect imitators in this brain formation weakens the alarm state in the test of "threatening situation" avoidance but is not effective in the test of "illuminated site" avoidance. On the contrary, the chemical stimulation of locus coeruleus by serotonin influences the anxiolytic effect in two different experimentally modelled states of alarm. The participation of locus coeruleus and acidergic mechanisms in anxiety of diverse aversive genesis is discussed.