RESUMO
Objective: In the present study, we aimed to examine the effects of repeated D-amphetamine (AMPH) exposure, a well-accepted animal model of acute mania in bipolar disorder (BD), and histone deacetylase (HDAC) inhibitors on locomotor behavior and HDAC activity in the prefrontal cortex (PFC) and peripheral blood mononuclear cells (PBMCs) of rats. Moreover, we aimed to assess brain-derived neurotrophic factor (BDNF) protein and mRNA levels in these samples. Methods: We treated adult male Wistar rats with 2 mg/kg AMPH or saline intraperitoneally for 14 days. Between the 8th and 14th days, rats also received 47.5 mg/kg lithium (Li), 200 mg/kg sodium valproate (VPT), 2 mg/kg sodium butyrate (SB), or saline. We evaluated locomotor activity in the open-field task and assessed HDAC activity in the PFC and PBMCs, and BDNF levels in the PFC and plasma. Results: AMPH significantly increased locomotor activity, which was reversed by all drugs. This hyperactivity was associated with increased HDAC activity in the PFC, which was partially reversed by Li, VPT, and SB. No differences were found in BDNF levels. Conclusion: Repeated AMPH administration increases HDAC activity in the PFC without altering BDNF levels. The partial reversal of HDAC increase by Li, VPT, and SB may account for their ability to reverse AMPH-induced hyperactivity. .
Assuntos
Animais , Masculino , Fator Neurotrófico Derivado do Encéfalo/análise , Dextroanfetamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Histona Desacetilases/análise , Atividade Motora/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Análise de Variância , Antimaníacos/farmacologia , Transtorno Bipolar/tratamento farmacológico , Transtorno Bipolar/metabolismo , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Ácido Butírico/farmacologia , Modelos Animais de Doenças , Histona Desacetilases/efeitos dos fármacos , Lítio/farmacologia , Córtex Pré-Frontal/metabolismo , Ratos Wistar , Reação em Cadeia da Polimerase em Tempo Real , Ácido Valproico/farmacologiaRESUMO
Buspirone, a partial agonist of 5-hydroxytryptamine autoreceptors, selectively blocks presynaptic nigrostriatal D2 dopamine (DA) autoreceptors. At doses which antagonised action of apomorphine in biochemical presynaptic nigrostriatal D2 DA autoreceptor test systems buspirone neither induced catalepsy nor antagonised apomorphine-induced turning behaviour in rats indicating that at these doses buspirone does not block postsynaptic striatal D2 and D1 DA receptors. This study determines whether at high doses buspirone blocks postsynaptic striatal D2 and D1 DA receptors and provides behavioural evidence for selective blockade of presynaptic nigrostriatal D2 DA autoreceptors by smaller doses of buspirone. We investigated in rats whether buspirone induces catalepsy and effect of its pretreatment on DA agonist induced oral stereotypies and on cataleptic effect of haloperidol and small doses (0.05, 0.1 mg/kg, ip) of apomorphine. Buspirone at 1.25, 2.5, 5 mg/kg, ip neither induced catalepsy nor antagonised apomorphine stereotypy but did potentiate dexamphetamine stereotypy and antagonised cataleptic effect of haloperidol and small doses of apomorphine. Buspirone at 10, 20, 40 mg/kg, ip induced catalepsy and antagonised apomorphine and dexamphetamine stereotypies. Our results indicate that buspirone at 1.25, 2.5, 5 mg/kg blocks only presynaptic nigrostriatal D2 DA autoreceptors while at 10, 20, 40 mg/kg, it blocks postsynaptic striatal D2 and D1 DA receptors. Furthermore, buspirone at 1.25, 2.5, 5 mg/kg by selectively blocking presynaptic nigrostriatal D2 DA autoreceptors, increases synthesis of DA and makes more DA available for release by dexamphetamine and during haloperidol-induced compensatory 'feedback' increase of nigrostriatal DAergic neuronal activity and thus potentiates dexamphetamine stereotypy and antagonizes haloperidol catalepsy.
Assuntos
Animais , Apomorfina/farmacologia , Buspirona/farmacologia , Catalepsia/induzido quimicamente , Dextroanfetamina/farmacologia , Antagonistas de Dopamina/farmacologia , Relação Dose-Resposta a Droga , Haloperidol/farmacologia , Masculino , Ratos , Ratos Wistar , Receptores de Dopamina D1/antagonistas & inibidores , Receptores de Dopamina D2/antagonistas & inibidores , Comportamento Estereotipado/efeitos dos fármacosRESUMO
Dextromethorphan, a noncompetitive blocker of N-methyl-D- aspartate (NMDA) type of glutamate receptor, at 7.5-75 mg/kg, ip did not induce oral stereotypies or catalepsy and did not antagonize apomorphine stereotypy in rats. These results indicate that dextromethorphan at 7.5-75 mg/kg does not stimulate or block postsynaptic striatal D2 and D1 dopamine (DA) receptors. Pretreatment with 15 and 30 mg/kg dextromethorphan potentiated dexamphetamine stereotypy and antagonised haloperidol catalepsy. Pretreatment with 45, 60 and 75 mg/kg dextromethorphan, which release 5-hydroxytryptamine (5-HT), however, antagonised dexamphetamine stereotypy and potentiated haloperidol catalepsy. Apomorphine stereotypy was not potentiated or antagonised by pretreatment with 7.5-75 mg/kg dextromethorphan. This respectively indicates that at 7.5-75 mg/kg dextromethorphan does not exert facilitatory or inhibitory effect at or beyond the postsynaptic striatal D2 and D1 DA receptors. The results are explained on the basis of dextromethorphan (15-75 mg/kg)-induced blockade of NMDA receptors in striatum and substantia nigra pars compacta. Dextromethorphan at 15 and 30 mg/kg, by blocking NMDA receptors, activates nigrostriatal dopaminergic neurons and thereby potentiates dexampetamine stereotypy and antagonizes haloperidol catalepsy. Dextromethorphan at 45, 60 and 75 mg/kg, by blocking NMDA receptors, releases 5-HT and through the released 5-HT exerts an inhibitory influence on the nigrostriatal dopaminergic neurons with resultant antagonism of dexampetamine stereotypy and potentiation of haloperidol catalepsy.
Assuntos
Animais , Antitussígenos/farmacologia , Apomorfina/farmacologia , Comportamento Animal/efeitos dos fármacos , Catalepsia/induzido quimicamente , Dextroanfetamina/farmacologia , Dextrometorfano/farmacologia , Dopamina/metabolismo , Agonistas de Dopamina/farmacologia , Antagonistas de Dopamina/farmacocinética , Inibidores da Captação de Dopamina/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Haloperidol/toxicidade , Masculino , Ratos , Ratos Wistar , Receptores Dopaminérgicos/efeitos dos fármacos , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Comportamento Estereotipado/efeitos dos fármacosRESUMO
This study aimed to examine the effects of haloperidol and amphetamine on human startle response modulated by emotionally-toned film clips. Sixty participants, in two groups [one receiving haloperidol and the other receiving amphetamine] were tested using electromyography [EMG] to measure eye-blink muscle [orbicular oculi] while different emotions were induced by six 2-minute film clips. An, affective rating shows the negative and positive effects of the two drugs on emotional reactivity, neither amphetamine nor haloperidol had any impact on the modulation of the startle response. The methodological and theoretical aspects of the study and findings will be discussed
Assuntos
Humanos , Masculino , Dextroanfetamina/farmacologia , Haloperidol/farmacologia , Psicoacústica , Eletromiografia , Piscadela , EmoçõesRESUMO
The effects of different doses of ondansetron (0.1, 0.5, 1, 2 mg/kg) administered intra-peritoneally were studied on amphetamine-induced hyperactivity and stereotypy in wistar rats. Ondansetron was administered 30 minutes prior to d-amphetamine (3 mg/kg, i.p.). Ondansetron in doses of 0.5 and 1 mg/kg significantly decreased the mean number of head dippings and crossings in the hole board test and in doses of 0.1 and 0.5 mg/kg significantly decreased the average stereotypic score. Since the hyperactivity and stereotypy are dopamine mediated, the effect of ondansetron to reduce these states suggests a potential role for ondansetron in conditions with dopamine excess.
Assuntos
Animais , Dextroanfetamina/farmacologia , Masculino , Atividade Motora/efeitos dos fármacos , Ondansetron/farmacologia , Ratos , Ratos Wistar , Receptores de Serotonina/fisiologia , Receptores 5-HT3 de Serotonina , Antagonistas da Serotonina/farmacologia , Comportamento Estereotipado/efeitos dos fármacosRESUMO
El comportamiento impulsivo, hiperactivo y con poca capacidad de atención en niños se considera un trastorno cuando éste es severo, inapropiado y altera las funciones en el hogar y en el colegio. Actualmente existen dos términos para denominar este trastorno: trastorno de déficit atencional con hiperactividad (TDAH) y trastorno hiperkinético (TH), término ya poco usado. Resulta a veces difícil distinguir el TDAH de otras patologías como por ejemplo: trastorno de conducta, trastornos emocionales, síndrome depresivo, problemas de aprendizaje, ya que éstos suelen asociarse a las características que presentan los niños con TDAH
Assuntos
Humanos , Criança , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Clonidina/uso terapêutico , Dextroanfetamina/administração & dosagem , Dextroanfetamina/farmacologia , Magnésio/uso terapêutico , Metilfenidato/administração & dosagem , Metilfenidato/farmacologia , PrognósticoRESUMO
Se analizaron 84 pacientes con las manifestaciones clínicas características del DAHI (Déficit Atencional con Hiperactividad y Excesiva Impulsividad) en un estudio de observación longitudinal a partir de 1983 hasta 1994 en el sector norte de Santiago. Se decidió incluir en el estudio a los pacientes referidos a la clínica ambulatoria de Neurología del Hospital Roberto del Río, durante el mencionado período, desde los Consultorios de Atención Primaria. En casi todos los casos se empleó dextroanfetamina (en casos justificados se empleó metilfenidato), que era entregada a los pacientes si asistían a los controles periódicamente, observándose un adecuado efecto terapéutico, con efectos adversos en pocos casos y sin evidencias de dependencia o aumento de tolerancia. A pesar de ser pacientes complicados desde el punto de vista biológico, económico y social, el plan terapeútico fue satisfactorio en términos generales, siendo los resultados más efectivos y consistentes en quienes la sintomatología del déficit atencional no se acompañaba de alteraciones conductuales, fueron menos favorables cuando hubo manifestaciones de disfunción cerebral orgánica y más problemáticos en la medida que habían evidencias de disfunción psicosocial en el entorno familiar. Los resultados sugieren que la dextroanfetamina puede ser considerada como favorable en una alta proporción de casos independientemente de las condiciones biológicas y del desarrollo psicomotor, pero fueron fundamentales la continuidad y adherencia al plan terapeútico, tanto el manejo ambiental y al uso adecuado del fármaco por parte del paciente y de la familia
Assuntos
Humanos , Masculino , Feminino , Pré-Escolar , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estudos Longitudinais , Adaptação Psicológica , Distribuição por Idade , Transtorno do Deficit de Atenção com Hiperatividade/complicações , Transtorno do Deficit de Atenção com Hiperatividade/etiologia , Dextroanfetamina , Dextroanfetamina/efeitos adversos , Dextroanfetamina/farmacologia , Deficiências da Aprendizagem , Metilfenidato/farmacologia , Instituições Acadêmicas , Distribuição por Sexo , Fatores Socioeconômicos , Resultado do TratamentoRESUMO
Effects of intrastriatal injections of haloperidol (Dopamine antagonist) and D-amphetamine (Dopamine agonist) on lordosis behaviour were studied in ovariectomized female albino rats, after priming with subcutaneous injections of estrogen and progesterone. The lordosis quotient (LQ) significantly increased after haloperidol, and decreased following D-amphetamine treatment. However, the inhibitory effect of D-amphetamine was transient and could be reversed by haloperidol in the same animal when given one hour after the D-amphetamine injection. The ovarian hormones probably act centrally to suppress the DA system in the striatum thereby enhancing the tonic and dorsal immobility responses associated with lordosis.
Assuntos
Animais , Corpo Estriado/fisiologia , Dextroanfetamina/farmacologia , Dopamina/metabolismo , Estradiol/farmacologia , Feminino , Haloperidol/farmacologia , Injeções Subcutâneas , Ovariectomia , Postura , Progesterona/administração & dosagem , Ratos , Comportamento Sexual Animal/efeitos dos fármacosRESUMO
The psychoactive drugs imipramine, chlorpromazine and lithium chloride inhibit tryptamine tetrazolium reductase activity in vitro by 68, 60 and 33% respectively at a concentration of 1 x 10(-3) M while amphetamine negligibly inhibits the enzyme activity. No change in enzyme activity is observed in vivo.
Assuntos
Animais , Encéfalo/efeitos dos fármacos , Cloretos/farmacologia , Clorpromazina/farmacologia , Dextroanfetamina/farmacologia , Imipramina/farmacologia , Lítio/farmacologia , Cloreto de Lítio , Masculino , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/antagonistas & inibidores , Psicotrópicos/farmacologia , RatosRESUMO
The work is aimed to compare the relative strength of dextroamphetamine and yogic meditation on the performance of 3 different groups of medical students to concentrate on the task to balance on a balance board. Group A subjects were mediators, group B subjects were given orally 5 and 10 mg of dextroamphetamine in a capsule, 1 hr prior to the test. Group C subjects were given same capsule but with lactose in place of the drug (placebo). This last groups served as control for the study. The balance index calculated taking into account their balance time and error score at each trial of 5 min duration showed that the performance of the group B (drug) had declined with overall percentile fall of 40.6% as compared to the performance of the controls (placebo) whereas, the performance of Group A (meditators) went on steadily and progressively increasing throughout the period of 10 trial days with overall percentile rise of 27.8%. The results were conclusive to confirm earlier reports that amphetamine is not of use for improvement of task rather, it deteriorates the task performance. Contrary to that, yogic meditation is of merit to achieve concentration for mental as well as physical task.
Assuntos
Adolescente , Adulto , Dextroanfetamina/farmacologia , Feminino , Humanos , Masculino , Músculos/efeitos dos fármacos , Equilíbrio Postural/efeitos dos fármacos , YogaRESUMO
1. The effects of ß-phenylethylamine (PEA) alone and in association with caroxazone, a potent inhibitor of monoamine oxidase B (MAO B), on the activity and long-term memory in the wheel-shaped activity monitor and on fixed-interval two-way avoidance acquisition were studied in rats. In a separate study, we determined the effects of PEA and of d-amphetamine on the variable-internal two-way avoidance acquisition. 2. The action of PEA was markedly different from that of aplhetamine in several aspects. The stimulating effects of PEA in the wheel-shaped activity monitor were of a more subtle nature than those of amphetamine and in the variable-interval two-way avoidance acquisition PEA had no effect, while amphetamine improved performance. 3. PEA did not induce an increase in path-choice stereotypy, but caroxazone did. The absence of any caroxazone-session interaction effects on the path interation frequency suggested that there were no long-term memory effects. 4. In the fixed-interval two-way avoidance acquisition experiments, PEA increased the avoidance responses of tats while caroxazone had no effect. The association of the two drugs did not potenciate either
Assuntos
Animais , Feminino , Ratos , Aprendizagem da Esquiva/efeitos dos fármacos , Dextroanfetamina/farmacologia , Oxazinas/farmacologia , Fenetilaminas/farmacologia , Interações Medicamentosas , Comportamento Exploratório/efeitos dos fármacos , Memória/efeitos dos fármacos , Atividade Motora/efeitos dos fármacos , Ratos EndogâmicosRESUMO
Se valoró el efecto de la hormona estimulante de melanocitos (MSH) sobre la atención selectiva en el hombre por medio de los cambios de amplitud en los componentes temprano y tardío de los potenciales somáticos evocados (PSE). Se tuvo cuidado especial de valorar los cambios concomitantes en el nivel de alerta general y en las pruebas de memoria reciente o de discriminación espacial. Este efecto se comparó con los producidos por fármacos del tipo de la noradrenalina (dextroanfetamina) y morfínicos (fentanil y naloxona). Ninguno de estos compuestos cambió la amplitud de los PSE tempranos, pero modificaron de manera diferencial los tardíos; la MSH y la naloxona aumentaron la amplitud de los PSE tardíos, en tanto que la dextroanfetamina y el fentanil la disminuyeron. La MSH y la naloxona aumentaron la velocidad de reacción, lo mismo que las pruebas de retención visual y discriminación espacial, sin cambios en el nivel de alerta general. La dextroanfetamina y el fentanil disminuyeron las pruebas de retención visual o de discriminación espacial, pero en tanto la primera aumentó la velocidad de reacción y el estado de alerta general, la última disminuyó la velocidad de reacción sin producir cambios en el estado de alerta general. Estos dados sugieren que MSH y otros compuestos relacionados producen cambios en el proceso de la atención del hombre al modificar la excitabilidad de los componentes tardíos de los PSE mediadores del sistema extralemniscal, pero no los propios del sistema lemnisco. Sugieren además que los cambios producidos en los PSE por MSH, fentanil y naloxona ocurrieron a nivel cortical pero no en la parte reticular del sistema extralemniscal, puesto que estos compuestos modificaron la velocidad de reacción y las pruebas de retención visual o de discriminación espacial (parte cortical) sin cambios en el nivel de alerta general (parte reticular). Sin embargo, los cambios producidos por la destroanfetamina en los PSE tardíos y la atención, deben considerarse consecuencias de la activación de los circuitos reticular y motor, que son independientes del relacionado con la atención selectiva