RESUMO
Rats were trained to self-stimulate the medial prefrontal cortex, a region rich in dopaminergic terminals. After the region adjacent to the electrode site was labeled with [14C]dopamine, it was perfused repeatedly by means of push-pull cannulas. Electrical stimulation of this cortical area in six animals enhanced the release of dopamine and its associated metabolites in nine of 16 experiments. Thus in vivo evidence is provided that dopamine is involved in the brain self-stimulation mechanism within the frontal cortex.
Assuntos
Córtex Cerebral/metabolismo , Dopamina/metabolismo , Lobo Frontal/metabolismo , Autoestimulação/fisiologia , Animais , Estimulação Elétrica , Masculino , RatosRESUMO
A bacterial pyrogen acts on the brain by disturbing the natural balance between two essential cations in the cerebral region involved in thermoregulation. After typhoid vaccine is administered to the unanesthetized cat, (45)Ca(2+) efflux into the third cerebral ventricle increases while (22)Na(+) is retained in hypothalamic tissue at the same time that the set-point temperature begins to rise. The subsequent rates of (22)Na(+) and (45)Ca(2+) efflux parallel the course of the bacterial fever but in a reciprocal fashion. This supports the theory that a change in the set-point temperature is determined by an alteration in the inherent ratio of Na(+) to Ca(2+) ions in the hypothalamus.
Assuntos
Cálcio/metabolismo , Febre/metabolismo , Hipotálamo/metabolismo , Sódio/metabolismo , Animais , Regulação da Temperatura Corporal , Cálcio/líquido cefalorraquidiano , Isótopos de Cálcio , Gatos , Ventrículos Cerebrais , Sódio/líquido cefalorraquidiano , Isótopos de Sódio , Vacinas Tíficas-Paratíficas/administração & dosagemRESUMO
The body temperature of many mammals is set at or around 37 degrees C. The mechanism for this set point appears to depend on a constant and inherent balance between sodium and calcium ions within the posterior hypothalamus. When this region is perfused in unanesthetized cats, an extracellular excess or a normal physiological concentration of sodium ions evokes a rise in body temperature if calcium is not in the perfusate. At the same site, an excess or normal concentration of calcium ions causes the temperature to fall when sodium is absent.
Assuntos
Regulação da Temperatura Corporal , Cálcio/fisiologia , Hipotálamo/fisiologia , Sódio/fisiologia , Animais , Gatos , Concentração Osmolar , Perfusão , Técnicas Estereotáxicas , SacaroseRESUMO
Tetrahydropapaveroline (THP), a dopamine-dopaldehyde condensation product, was delivered directly into the cerebral ventricle of rats automatically every 15 minutes for 12 days. The animals were given access to both water and ethylalcohol, the latter being presented in 12 concentrations from 3 to 30 percent. Within 3 to 6 days of the start of the infusion of THP, the rats, which normally rejected alcohol, drank alcohol solutions in increasingly excessive amounts; this was accompanied by symptoms that were similar to those of withdrawal and intoxication. These results provide evidence that an abnormal metabolite in the brain may produce the addictive state caused by alcoholic beverages.
Assuntos
Consumo de Bebidas Alcoólicas , Química Encefálica , Papaverina/análogos & derivados , Animais , Aminas Biogênicas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Injeções Intraventriculares , Papaverina/farmacologia , Ratos , Estereoisomerismo , Síndrome de Abstinência a Substâncias/induzido quimicamenteRESUMO
When perfusate is collected from the anterior hypothalamus of a cooled donor monkey and is transfused to a corresponding hypothalamic site in a normal monkey, fever occurs in this recipient. Conversely, perfusate from a heated donor monkey lowers the recipient monkey's temperature when the same hypothalamic transfusion procedure is followed. These experiments provide direct evidence of a neurochemical "coding" within the specific anatomical region of the brain historically implicated in the control of body temperature.
Assuntos
Regulação da Temperatura Corporal , Líquido Cefalorraquidiano , Hipotálamo/fisiologia , Neurotransmissores/fisiologia , Animais , Febre/induzido quimicamente , Haplorrinos , Masculino , Perfusão , Técnicas EstereotáxicasRESUMO
Preference for ethyl alcohol was significantly reduced or totally abolished in rats given orally p-chlorophenylalanine, a tryptophan hydroxylase inhibitor that selectively depletes brain serotonin. Some aversion to alcohol was observed while p-chlorophenylalanine was administered, but the rats' rejection of alcohol was even more marked after the drug was discontinued. Oral administration of alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor that depletes brain catecholamines, slightly reduced selection of alcohol, but preference returned to normal as soon as alpha-methyl-p-tyrosine was terminated.
Assuntos
Encéfalo/metabolismo , Aprendizagem por Discriminação/efeitos dos fármacos , Etanol/farmacologia , Fenilalanina/farmacologia , Serotonina/metabolismo , Alcoolismo/tratamento farmacológico , Animais , Encéfalo/efeitos dos fármacos , Depressão Química , Humanos , Masculino , Metiltirosinas/farmacologia , Oxigenases de Função Mista/antagonistas & inibidores , Psicofarmacologia , Ratos , TriptofanoRESUMO
Noradrenergic neurons in the hypothalamus involved in feeding and satiety are activated by gastrointestinal receptors. In the unrestrained rat, sites were first identified at which norepinephrine injected in the medial hypothalamus caused spontaneous feeding, or in the lateral hypothalamus caused no response. The activity of in vivo norepinephrine at these two sites was characterized by localized push-pull perfusion. When a nutrient was infused directly into the rat's duodenum, the synaptic release of hypothalamic norepinephrine was enhanced at lateral sites insensitive to norepinephrine, but suppressed at medial sites reactive to norepinephrine. Thus, signals from duodenal receptors are conceivably sent to the rat's brain to end feeding by way of noradrenergic inhibitory neurons in the hypothalamus.
Assuntos
Duodeno/fisiologia , Hipotálamo/fisiologia , Norepinefrina/fisiologia , Saciação/fisiologia , Resposta de Saciedade/fisiologia , Animais , Duodeno/inervação , Comportamento Alimentar/fisiologia , Glucose , Ratos , Fatores de TempoRESUMO
When the concentration of calcium ions in the cerebral ventricles is elevated, a fully satiated rat eats voraciously. This feeding response is not prevented by prior intraventricular administration of alpha-or beta-adrenergic blocking agents, or other pharmacological antagonists. This supports the concept of an independent ionic mechanism, rather than a neurotransmitter one, for modulating a "set-point" for weight or hunger.
Assuntos
Química Encefálica , Cálcio/farmacologia , Comportamento Alimentar/efeitos dos fármacos , Animais , Apetite/efeitos dos fármacos , Cálcio/administração & dosagem , Ventrículos Cerebrais , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Injeções , Masculino , Norepinefrina/farmacologia , Fentolamina/farmacologia , Propranolol/farmacologia , Ratos , Ratos EndogâmicosRESUMO
Serious controversy pervades the scientific study of radio-frequency (RF) radiation and its biological effects. The issues range broadly from international differences in safe exposure standards to questions pertaining to the neurological symptoms purportedly induced by electromagnetic radiation. In a more specialized vein, there is great concern in the discipline about the influence of different sources of radiation on the activity of calcium in the brain. A principal and very realistic reason for this concern stems from the pivotal importance of calcium ions in the normal functioning of the brain in all of its myriad complexity. The purpose of the review is to critically evaluate from an unbiased and "non-involved" viewpoint the major findings on the possible interaction between calcium ions and various radiation sources. Background information is also considered as it relates even indirectly to hypothetical mechanisms that might be used to explain any possible shift in Ca++ ion kinetics. Finally, an inclusive critique is presented which deals with the bench-top methods and strategy used in the conduct of calcium-radiation experiments.
Assuntos
Encéfalo/efeitos da radiação , Cálcio/metabolismo , Animais , Comportamento Animal , Barreira Hematoencefálica , Temperatura Corporal , Encéfalo/fisiologia , Membrana Celular/metabolismo , Cóclea/fisiologia , Febre/fisiopatologia , Audição/efeitos da radiação , Canais Iônicos/metabolismo , Cinética , Micro-Ondas , Neurônios/fisiologia , Neurotransmissores/fisiologiaRESUMO
The complex role of dopamine (DA) in the diencephalic mechanisms involved in the control of body temperature is reviewed and evaluated. In the context of the monoamine theory of thermoregulation, catecholaminergic synapses in the anterior hypothalamic pre-optic area, are proposed mediate the pathways in the brain-stem which subserve heat dissipation. Within this theoretical framework, hypothalamic DA is considered to underlie a portion of the functional component of the heat loss system. This deduction is based on pharmacological studies in which both the catecholamine and receptor antagonists have been infused directly into the hypothalamus. In view of the action of DA applied to the substantia nigra and other subcortical structures, the unique anatomical circuitry of the central dopaminergic projections has also been analyzed in terms of specific connections within critical morphological regions related to thermal functions. In particular, the nigro-striatal pathway could be involved in the mediation of one or more of the different aspects of the thermoregulatory system integrating both autonomic and behavioral responses. Finally, an anatomical schema which portrays the suggested mechanisms of DA activity is presented.
Assuntos
Regulação da Temperatura Corporal , Encéfalo/fisiologia , Dopamina/fisiologia , Animais , Regulação da Temperatura Corporal/efeitos dos fármacos , Mapeamento Encefálico , Gatos , Núcleo Caudado/efeitos dos fármacos , Dopamina/farmacologia , Haplorrinos , Humanos , Hipotálamo Anterior/efeitos dos fármacos , Microinjeções , Vias Neurais/fisiologia , Núcleo Accumbens/efeitos dos fármacos , Bulbo Olfatório/efeitos dos fármacos , Coelhos , Especificidade da Espécie , Substância Negra/efeitos dos fármacos , Transmissão SinápticaRESUMO
Over the last 30 years, studies of the in vivo activity of neurotransmitters and other endogenous factors in the brain have comprised a major effort in the neurosciences. Historically, the technology of push-pull perfusion was utilized as a major approach to investigations in this field. In the last 10 years, cerebral dialysis has been used as an alternative method essentially for the same scientific purpose, since the perfusion technique was viewed as difficult and excessively damaging to tissue. This review considers the representative literature in which both systems have been used to study local neurochemical responses to a drug or other chemical factor, a physiological condition or other situation. In addition, new experiments have been undertaken to compare, in the same animal and at the same time, the utility and properties inherent in the techniques of push-pull perfusion and cerebral dialysis in terms of the profile of a neurotransmitter activity and their local histopathological effects. A miniaturized 33/26 ga push-pull needle and a 24 ga dialysis probe were implanted simultaneously in the left and right caudate nuclei, respectively, in the anesthetized rat. An artificial cerebrospinal fluid (CSF) was perfused simultaneously through both devices at a rate of 10 microliters/min in the push-pull cannula and at 1.0 or 2.0 microliters/min in the dialysis probe. Within a series of 8-10 successive perfusions, excess K+ ions in a concentration of either 30 or 60 mM were incorporated in the CSF and delivered simultaneously to both the push-pull cannula and dialysis probe. Samples of perfusate and dialysate were assayed chromatographically by coulometric HPLC detector and quantitated in terms of the pg/min efflux of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA). The results showed that the resting level of DA was almost undetectable in dialysate samples from either structure; in push-pull perfusates the recovery of DA ranged between 7.0 to 10.0 pg/min, which was increased threefold by excess K+ ions. The recovery of DA and the three metabolites in samples of push-pull perfusate was two to four times that in samples of dialysate during the condition of excess K+ ions. Post-mortem histological analysis of the sites of perfusion and dialysis revealed little or no differences in the cytological damage induced by either the perfusion needle or dialysis probe. Finally, the advantages and limitations of each of these two experimental approaches to in vivo analysis of neurotransmitter efflux are reviewed in relation to the selection of an open or closed system for the on-line study of in vivo neurochemical events.
Assuntos
Química Encefálica/fisiologia , Diálise/métodos , Perfusão/métodos , Animais , Diálise/instrumentação , Neurotransmissores/análise , Neurotransmissores/metabolismo , Perfusão/instrumentação , RatosRESUMO
The role of a prostaglandin of the E series (PGE) in the hypothalamic mechanisms underlying a fever continues to be controversial. This paper reviews the historical literature and current findings on the central action of the PGEs on body temperature (Tb). New experiments were undertaken to examine the local effect of muscarinic, nicotinic, serotonergic, alpha-adrenergic, or beta-adrenergic receptor antagonists at hypothalamic sites where PGE1 caused a rise in Tb of the primate. Guide tubes for microinjection were implanted stereotaxically above sites in and around the anterior hypothalamic, preoptic area (AH/POA) of male Macaque monkeys. Following postoperative recovery, 30-100 ng of PGE1 was micro-injected unilaterally in a volume of 1.0-1.5 microliter at sites in the AH/POA to evoke a rise in Tb, and once identified, pretreated with a receptor antagonist. PGE1 hyperthermia was significantly reduced by microinjections of the muscarinic and nicotinic antagonists, atropine, or mecamylamine, at PGE1 reactive sites in the AH/POA. The serotonergic antagonist, methysergide, injected at PGE1 sensitive sites in the ventromedial hypothalamus also attenuated the rise in Tb. However, the 5-HT reuptake blocker, fluoxetine, and the beta-adrenergic receptor antagonist, propranolol, injected in the AH/POA failed to alter the PGE1 hyperthermia. In contrast, the alpha-adrenergic antagonist, phentolamine, potentiated the increase in Tb at all PGE1 reactive sites in the hypothalamus. An updated model is presented to explain how the concurrent actions of aminergic neurotransmitters acting on their respective receptors in the hypothalamus can interact with a PGE to elicit hyperthermia. Finally, an evaluation of the current literature including recent findings on macrophage inflammatory protein (MIP-1) supports the conclusion that a PGE in the brain is neither an obligatory nor essential factor for the expression of a pyrogen fever.
Assuntos
Regulação da Temperatura Corporal/efeitos dos fármacos , Hipotálamo/fisiologia , Prostaglandinas E/farmacologia , Receptores de Neurotransmissores/efeitos dos fármacos , Antagonistas Adrenérgicos alfa/farmacologia , Antagonistas Adrenérgicos beta/farmacologia , Animais , Antagonistas Colinérgicos , Hipotálamo/anatomia & histologia , Hipotálamo/efeitos dos fármacos , Hipotálamo Anterior/anatomia & histologia , Hipotálamo Anterior/fisiologia , Injeções Intraventriculares , Macaca mulatta , Macaca nemestrina , Masculino , Microinjeções , Área Pré-Óptica/anatomia & histologia , Área Pré-Óptica/fisiologia , Prostaglandinas E/administração & dosagem , Antagonistas da Serotonina , Núcleo Hipotalâmico Ventromedial/anatomia & histologia , Núcleo Hipotalâmico Ventromedial/fisiologiaRESUMO
In two groups of male rats having an average age of either 90 days or two years, guide cannulae for bilateral push-pull perfusion were implanted stereotaxically to rest upon the superficial frontal cerebral cortex. On post-operative recovery, either 1.5 or 3.0 g/kg 20% ethanol (V/V) was given by intragastric gavage to each unrestrained rat. Sequential samples of venous blood were obtained from the tail and analyzed for alcohol levels by gas chromatography. A set of push-pull perfusions of the cortical sites was carried out with an artificial CSF before gavage and at 25, 50 and 150 min after the administration of ethanol. An individual perfusion was continued for 5.0 min at a rate of 25 microliters/min. Using high performance liquid chromatography with electrochemical detection (HPLC-EC) each sample of perfusate was then assayed for its content of glutamate (Glu), aspartate (Asp), glutamine (Gln), glycine (Gly), taurine (Tau) and GABA with homoserine used as the internal standard. The results showed that the 3.0 g/kg dose of ethanol resulted in a higher level of blood ethanol in the older animals, which persisted over the 150 min time interval. Further, the 1.5 g/kg dose of ethanol administered to the older rats reduced the cortical activity of Glu and Gln relative to the younger animals. In addition, the 3.0 g/kg dose augmented the cortical efflux of Tau in the aged rats. Neither dose of ethanol affected the efflux of Asp or Gly from the perfused frontal cortex of either the young or old group, nor was the release of GABA detectable under either the control condition or following treatment with ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Aminoácidos/metabolismo , Etanol/farmacologia , Lobo Frontal/efeitos dos fármacos , Neurotransmissores/metabolismo , Fatores Etários , Animais , Glutamatos/metabolismo , Ácido Glutâmico , Glutamina/metabolismo , Masculino , Ratos , Ratos Endogâmicos , Taurina/metabolismo , Ácido gama-Aminobutírico/metabolismoRESUMO
The selectively bred high alcohol drinking (HAD) line of rat is considered as a potential model of one type of alcoholism. The purpose of the present experiments was to compare the efficacy of two drugs on the volitional drinking of the HAD rats: the 5-HT2A receptor antagonist, amperozide, and a nonselective antagonist of opiate receptors, naltrexone. To determine the pattern of alcohol drinking of the HAD rats, a standard preference test was used in which water was offered with alcohol increased in concentrations from 3% to 30% over 11 days. The maximally preferred concentration of alcohol of each rat was offered for 4 days and ranged from 7% to 20% with a mean intake of 6.9 g/kg per day. Initially, 1.0 mg/kg amperozide, 2.5 mg/kg naltrexone, or the saline vehicle were injected twice daily for 4 days at 1600 and 2200 hours. Secondly, 2.0 mg/kg amperozide, 5.0 mg/kg naltrexone, or the saline vehicle were administered also for 4 days. After the drug sequences, alcohol preference tests continued for another 4 days. Whereas the saline vehicle was without effect on drinking, the administration of either drug caused a significant dose-dependent reduction in the daily intake of alcohol by the HAD rats in terms of absolute g/kg and proportion of alcohol to water consumed. A comparison of the drinking response to the higher doses of the two drugs showed that amperozide was more efficacious in suppressing alcohol intake than naltrexone. Niether amperozide nor naltrexone exerted any significant effects on food and water intakes or on body weight. These results support the concept of a functional link in the brain between the serotonergic and opioidergic systems postulated to underlie, in part, the aberrant drinking of alcohol. A marked dissociation between the temporal patterns of drinking after naltrexone and amperozide treatment suggests that the opiate receptors mediate the immediate reinforcing effects of alcohol, whereas the more vegetative phenomena underlying addictive properties of alcohol are regulated by 5-HT2A receptors postsynaptic to serotonergic neurons. Finally, the inhibitory actions of both drugs imply that multiple receptor mechanisms within the mesolimbic and other systems in the brain underpin the addictive liability to alcohol.
Assuntos
Dissuasores de Álcool/farmacologia , Consumo de Bebidas Alcoólicas/psicologia , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologia , Piperazinas/farmacologia , Antagonistas da Serotonina/farmacologia , Consumo de Bebidas Alcoólicas/genética , Animais , Relação Dose-Resposta a Droga , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Etanol/sangue , Masculino , Ratos , Ratos Endogâmicos , Fatores de TempoRESUMO
A number of cytokines including the family of interleukins and the macrophage inflammatory proteins act in the brain to produce fever. The purpose of this study was to determine whether the recently discovered hematopoietic progenitor cell stimulator, interleukin-11 (IL-11), alters the body temperature (Tb) of the rat when the cytokine is delivered directly to the thermosensitive and pyrogen reactive region of the hypothalamus. A guide cannula for micro-injection into the anterior hypothalamic pre-optic area (AH/POA) was implanted stereotaxically in each of 19 male Sprague-Dawley rats. A Mini-mitter transmitter for continuous monitoring of Tb of the animal was implanted i.p. Following postoperative recovery, recombinant human IL-11 was micro-injected in a volume of 1.0 microliter into the AH/POA in a dose of 2.7, 13.5, 27 or 250 ng. rhuIL-11 evoked a dose dependent fever with a mean rise in Tb of 0.91 +/- 0.06 degrees C, 1.68 +/- 0.11 degrees C and 0.99 +/- 0.08 degrees C following 13.5 ng, 27 ng and 250 ng, respectively. No significant change in Tb of the rats was produced by 2.7 ng IL-11 or the CSF control vehicle. A significant decline in the intake of food occurred also after the micro-injection of the 27 ng of IL-11. Prior treatment of the rat with 5.0 mg/kg of a prostaglandin synthesis inhibitor, indomethacin, administered intraperitoneally attenuated significantly the febrile response induced by the 250 ng dose of IL-11. These results demonstrate that IL-11 possesses potent thermogenic properties when acting within the ventral forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Febre/induzido quimicamente , Indometacina/farmacologia , Interleucina-11/farmacologia , Área Pré-Óptica/fisiologia , Animais , Temperatura Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Febre/prevenção & controle , Humanos , Interleucina-11/administração & dosagem , Interleucina-11/antagonistas & inibidores , Masculino , Microinjeções , Área Pré-Óptica/anatomia & histologia , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologiaRESUMO
In order to examine the central mechanism of pyrexic action of macrophage inflammatory protein-1 (MIP-1), guide cannulae for injections were implanted stereotaxically just above the anterior hypothalamic, pre-optic area of the rat. Following post-operative recovery, the body temperature (Tb) of each rat was monitored by a colonic thermistor probe over a test interval of 4 hr. Injected in a 0.5 microliter volume into the anterior hypothalamic pre-optic area, MIP-1, in a dose of 5.6 or 28 pg, evoked an intense fever with a latency of 15-30 min. Pretreatment of the anterior hypothalamic pre-optic area with 1.0 microgram cyclosporine A (CsA), delivered in a volume of 0.5 microliter, delayed the onset of the fever induced by 5.6 pg MIP-1, injected at the same site. Similar injections of CsA also attenuated significantly the magnitude of the fever, following either the 5.6 or 28 pg dose of MIP-1. As a systemic control, 15 mg/kg CsA was administered intraperitoneally, 2.0 hr before the injection of MIP-1 in the anterior hypothalamic pre-optic area. By this route, CsA also delayed the rise in temperature but the fever induced by 5.6 pg MIP-1 reached the same magnitude as that after MIP-1 alone. Conversely, intraperitoneal administration of CsA did not antagonize the pyrexic response evoked by 28 pg MIP-1, injected into the anterior hypothalamic pre-optic area, but rather enhanced the fever.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Temperatura Corporal/efeitos dos fármacos , Ciclosporina/farmacologia , Citocinas/farmacologia , Febre/fisiopatologia , Hipotálamo/fisiologia , Monocinas/farmacologia , Área Pré-Óptica/fisiologia , Animais , Mapeamento Encefálico , Quimiocina CCL4 , Ciclosporina/administração & dosagem , Citocinas/administração & dosagem , Febre/induzido quimicamente , Hipotálamo/efeitos dos fármacos , Proteínas Inflamatórias de Macrófagos , Monocinas/administração & dosagem , Área Pré-Óptica/efeitos dos fármacos , Ratos , Ratos Endogâmicos , Técnicas EstereotáxicasRESUMO
Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 microM harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (Tb) induced by 5.0 mg/kg harman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the harman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered Tb significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Química Encefálica/efeitos dos fármacos , Harmina/análogos & derivados , Hipocampo/metabolismo , Neurotoxinas/farmacologia , Serotonina/metabolismo , Antagonistas Adrenérgicos beta/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Fenclonina/farmacologia , Harmina/líquido cefalorraquidiano , Harmina/farmacologia , Hipocampo/efeitos dos fármacos , Ácido Hidroxi-Indolacético/líquido cefalorraquidiano , Ácido Hidroxi-Indolacético/metabolismo , Masculino , Microdiálise , Neurotoxinas/líquido cefalorraquidiano , Pindolol/farmacologia , Ratos , Ratos Sprague-Dawley , Serotonina/líquido cefalorraquidiano , Serotoninérgicos/farmacologiaRESUMO
In male rats of the Long-Evans strain, either 7.0 mg/kg of trimethyltin (TMT) or 0.9% NaCl was administered by intragastric gavage. After a period of recovery from the typical signs of trimethyltin toxicity, each rat was tested at 72-hr intervals for its locomotor activity in an open field apparatus, the floor of which was divided into square grids. The baseline activity of each of the trimethyltin-treated rats was significantly greater than the saline-treated controls. d-Amphetamine, injected intraperitoneally in a dose of 0.5 or 2.0 mg/kg, augmented the hyperactivity of the trimethyltin-treated animals. However, a 4.0 mg/kg dose of d-amphetamine markedly attenuated the hyperactivity of trimethyltin-treated rats while elevating that of the controls. Since trimethyltin produced an autism-like behavioral disorder involving hyperactivity, preservation, aggressiveness and impairment in problem-solving and memory function, the placating effect of amphetamine supports the proposition that the pathology due to trimethyltin may represent an experimental analogue to the hyperkinetic syndrome in children.
Assuntos
Dextroanfetamina/farmacologia , Atividade Motora/efeitos dos fármacos , Compostos de Trialquitina/antagonistas & inibidores , Compostos de Trimetilestanho/antagonistas & inibidores , Animais , Modelos Animais de Doenças , Humanos , Hipercinese/induzido quimicamente , Hipercinese/tratamento farmacológico , Masculino , RatosRESUMO
The release of both endogenous and newly synthesized amino acid neurotransmitters was examined simultaneously in different areas of the cerebral cortex in the freely moving rat. An array of push-pull guide tubes was implanted permanently to rest above the frontal, parietal, temporal and occipital areas of the cortex of each rat. Then a new double-lumen catheter system, specially adapted for localized push-pull perfusion of the conscious animal, was used to perfuse an artificial cerebrospinal fluid at each cortical site. For the new synthesis experiments, 0.5 microCi of [14C]glucose in a volume of 2.0 microliter was first microinjected into the perfusion site as a precursor to label amino acids. After the site was perfused at a rate of 12.0 microliter/min, each of the samples was assayed by two-dimensional thin-layer chromatography. In a second analysis, the content of six endogenous amino acids present in unlabeled samples of push-pull perfusate was quantified by high-performance liquid chromatography analysis with electrochemical detection. The results showed a notable homogeneity among each of the four cortical areas in the content of four of the six amino acids examined. Endogenous glutamine exhibited the highest proportional content in the cortical perfusates, whereas glutamic acid was proportionally higher in terms of new synthesis. An anatomical analysis revealed that the level of endogenous glutamic acid in the frontal area was significantly lower than that found in the occipital or temporal regions of the rat's cortex. An opposite result was obtained when the proportional synthesis of glutamic acid from [14C] glucose was compared in different cortical regions in that a statistically higher release occurred in the frontal than in the occipital cortex.
Assuntos
Cateterismo/métodos , Córtex Cerebral/análise , Neurotransmissores/análise , Aminoácidos/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Feminino , Glucose/metabolismo , Masculino , Ratos , Ratos EndogâmicosRESUMO
To determine whether endogenous dopamine is involved in the impairment of body temperature induced by neurotensin, the local activity of [14C]dopamine in the hypothalamus of the unanesthetized rat was examined. A push-pull guide tube was implanted permanently above an intended site of perfusion within the anterior hypothalamic, pre-optic area or other region of the diencephalon. After the endogenous stores of dopamine at a specific site were labelled by microinjection of 0.02-0.05 muCi of [14C]dopamine, an artificial cerebrospinal fluid was perfused at the site at a rate of 20 microliter/min and at successive 5 min intervals. Perfusion of neurotensin in concentrations of 0.05 or 0.1 microgram/microliter in the dorsomedial hypothalamus, lateral hypothalamus, arcuate nucleus or diagonal band of Broca evoked a calcium-dependent efflux of [14C]dopamine. The release of dopamine induced by neurotensin was functionally specific since it was: (1) not mimicked by the relatively inactive neurotensin analogue, [D-Arg9]neurotensin; (2) dependent on the morphological locus of the push-pull perfusion; and (3) not accompanied by an efflux of [3H]norepinephrine when the site was double-labelled. Although neurotensin perfused in the anterior hypothalamic, pre-optic area caused a consistent decline in temperature, in most cases the temperature change did not correlate with an enhanced release of dopamine. Moreover, the release of dopamine, but not the temperature change, was abolished when neurotensin was perfused in a calcium-free medium. These results show that it is unlikely that the thermolytic action of neurotensin, at least within the hypothalamus, is mediated by the presynaptic release of dopamine.