RESUMO
Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean +/- SEM, pg/20 microl, was 3.0 +/- 0.4 for LDS, 3.8 +/- 0.3 for HDS and 6.4 +/- 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (+/-)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500%) as compared with LDS (248%) or RDS (243%) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900% in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line.
Assuntos
8-Hidroxi-2-(di-n-propilamino)tetralina/farmacologia , Encéfalo/efeitos dos fármacos , Fenfluramina/farmacologia , Receptores de Serotonina/metabolismo , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Agonistas do Receptor de Serotonina/farmacologia , Serotonina/metabolismo , Análise de Variância , Animais , Encéfalo/metabolismo , Cruzamento , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipotermia/metabolismo , Microdiálise , Ratos , Receptores 5-HT1 de Serotonina , Especificidade da EspécieRESUMO
Breeding for high and low hypothermic responses to systemic administration of a serotonin1A (5-HT1A) receptor agonist (8-hydroxy-2-(di-n-propylamino)tetralin, 8-OH-DPAT) has resulted in high DPAT-sensitive (HDS) and low DPAT-sensitive (LDS) lines of rats, respectively. These lines also differ in several behavioral measures associated with stress. In the present microdialysis study we observed that basal 5-HT concentrations in the prefrontal cortex and dorsal hippocampus did not differ significantly between HDS and LDS rats. Thus, behavioral differences between the HDS and LDS lines might not be attributed to differences in basal 5-HT release. However, both lines had lower basal levels of 5-HT release than their randomly bred control group (random DPAT-sensitive, RDS) in the prefrontal cortex (mean ± SEM, pg/20 æl, was 3.0 ± 0.4 for LDS, 3.8 ± 0.3 for HDS and 6.4 ± 0.6 for RDS; F(2,59) = 5.8, P<0.005). The administration of (±)-fenfluramine (10 mg/kg) induced a greater increase in hippocampal 5-HT levels in HDS rats (500 percent) as compared with LDS (248 percent) or RDS (243 percent) rats (P<0.0001). There were no significant differences in the prefrontal cortex among lines, with a fenfluramine-induced 5-HT increase of about 900 percent in the three groups. This differential response to fenfluramine may be due to functional alterations of hippocampal 5-HT reuptake sites in the HDS line
Assuntos
Animais , Ratos , 8-Hidroxi-2-(di-n-propilamino)tetralina , Encéfalo , Fenfluramina , Receptores de Serotonina , Serotonina , Agonistas do Receptor de Serotonina , Inibidores Seletivos de Recaptação de Serotonina , Análise de Variância , Encéfalo , Cruzamento , Córtex Cerebral , Hipocampo , Hipotermia , Microdiálise , Especificidade da EspécieRESUMO
Pharmacological, neurochemical, and behavioral techniques were used to characterize DA-ACh interaction within the lateral hypothalamus (LH) in the context of locomotion, feeding behavior, and reinforcement. In Experiment 1, the muscarinic agonist carbachol injected in the LH increased locomotor activity in proportion to dose. In Experiment 2, the same doses of carbachol proportionately increased exctracellular DA in the nucleus accumbens (Nac) as monitored by brain microdialysis. Dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) also increased. In Experiment 3, LH infusion by reverse microdialysis of the D(2) receptor blocker sulpiride released ACh in the LH in a dose-response manner. This suggested that sulpiride disinhibits ACh release via D(2) receptors in the LH and thereby facilitates behavior. Confirming this in Experiment 4, local LH atropine 5 min before sulpiride suppressed the locomotor response to sulpiride for about 20 min. These results suggest that sulpiride acts in the LH by disinhibiting a hypothalamic locomotor mechanism that is cholinergically driven and connected with the mesoaccumbens dopamine pathway. Given prior results that local sulpiride in the LH can induce hyperphagia and reward, this system may be involved in searching for food and rewarding feeding behavior. In conclusion, DA acts in the LH via D(2) receptors to inhibit cholinergic neurons or terminals that are part of an approach system for eating.
Assuntos
Acetilcolina/fisiologia , Dopamina/fisiologia , Região Hipotalâmica Lateral/fisiologia , Locomoção/fisiologia , Animais , Atropina/administração & dosagem , Carbacol/administração & dosagem , Carbacol/farmacologia , Agonistas Colinérgicos/administração & dosagem , Agonistas Colinérgicos/farmacologia , Antagonistas de Dopamina/administração & dosagem , Antagonistas de Dopamina/farmacologia , Interações Medicamentosas , Comportamento Alimentar/efeitos dos fármacos , Comportamento Alimentar/fisiologia , Região Hipotalâmica Lateral/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Masculino , Microinjeções , Ratos , Ratos Sprague-Dawley , Reforço Psicológico , Sulpirida/administração & dosagem , Sulpirida/farmacologiaRESUMO
Many experimental designs require the chronic implantation of different elements destined to act as channels that facilitate the information conveyance between the brain and some external devices or vice versa. Electrodes for electrophysiological or electrochemical recording or brain stimulation, and guide shafts for drug administration or chemical monitoring of the extracellular space are the most common examples of channels serving those purposes. The stereotaxic implantation of one or more of those experimental tools in the same antero-posterior plane is relatively easy, but surgery is nonetheless more complicated when two or more elements have to be placed using totally different coordinates. In those cases the current strategy consists in the successive implantation of the elements, waiting for the hardening of the dental acrylic destined to fix one of them in place before dealing with the next. This procedure takes time, is considerably more laborious than surgery for single elements and is particularly difficult when the elements have to be implanted in close proximity. The present report describes a method that simplifies surgery for multiple intracerebral implantation and allows the simultaneous and exact placement of as many electrodes or guide shafts as is practical in any experimental design. The method requires the previous construction of a jig or template designed to temporarily hold the elements to be implanted, allowing them to assume and keep the same positional relationship that they should have when definitively in place within the skull. The design may vary according to the type of elements to be implanted and the coordinates required for each particular experiment, but here it is illustrated describing the assembly of a particular jig for the simultaneous implantation of guide shafts for ulterior microdialysis in the prefrontal cortex (PFC), nucleus accumbens (NAC) and striatum (STR). Some rules can be derived from this particular case to make the method a more general one and suitable for any combination of elements and stereotaxic coordinates.
Assuntos
Química Encefálica/fisiologia , Microdiálise/métodos , Animais , Encéfalo/anatomia & histologia , Microdiálise/instrumentação , Próteses e Implantes , Ratos , Técnicas EstereotáxicasRESUMO
This article describes the construction of a functional quadruple fluid swivel with low propensity to leaking and low resistance to rotation. It was obtained through the addition of a fourth channel and some modifications performed on the rotary unit of a triple channel fluid swivel recently described. Those modifications included alterations of the Touhey-Borst adapter (Becton-Dickinson), and the development of a new method of fixation of the rotary tubes to the rotary unit of the swivel using nuts and screws. With those improvements the former swivel was transformed in a still more versatile device that can be used in experimental designs requiring the use of this relatively high number of channels. It can be used, for instance, in simultaneous off-line brain microdialysis of up to four different areas or on-line brain microdialysis in two areas; in push-pull perfusions of two brain regions; in studies determining the neuropharmacokinetics and pharmacodynamics of any compound and combining continuous drug infusion through one channel, double brain microdialysis to describe the distribution characteristics of the drug into the central nervous system as well as to monitor the neurochemical modifications induced by the drug, and continuous plasma sampling to know the plasma pharmacokinetics of the drug. These and several other methods used in neuroscience research can also be combined using the swivel described here.
Assuntos
Encéfalo/fisiologia , Microdiálise/instrumentação , Perfusão/instrumentação , Farmacocinética , Farmacologia/instrumentação , Animais , Desenho de Equipamento , Microdiálise/métodos , Perfusão/métodos , Farmacologia/métodosRESUMO
Neurochemical changes in the rat lateral hypothalamus during drinking were assessed in 20 min sampling intervals, using in vivo brain microdialysis. Water-deprived animals drank (11 +/- 1 ml) during the hour that water was available. Drinking was maximal (7.8 +/- 0.7 ml) during the first 20 min after water presentation and minimal during the last 20 min (0.5 +/- 0.4 ml). There was a local enhancement in DA turnover evidenced by an increase in the extracellular levels of dopamine (DA) (155 +/- 47% during the second sample after water presentation as compared to predrinking levels) and dihydroxyphenyl acetic acid (DOPAC) (132 +/- 9.7% in the sample that followed water removal). There was also an initial increase in the acetylcholine (ACh) release (145.1 +/- 21.7%) during the first 20 min after water presentation followed by a reduction (50.12 +/- 18%) 20 min later. These changes are congruous with previously published results suggesting that both neurochemical systems are involved in the regulation of water intake. Considering that the exogenous administration of cholinergic drugs in this hypothalamic area elicits drinking, the initial increase in ACh release could be interpreted as one of the neurochemical events driving this behavior. Since the local blockade of D2 receptors has been shown to result in drinking the progressive increase in DA turnover detected in this study, as well as the concomitant reduction in ACh release, could be involved in drinking attenuation.
Assuntos
Acetilcolina/metabolismo , Dopamina/metabolismo , Comportamento de Ingestão de Líquido/fisiologia , Região Hipotalâmica Lateral/metabolismo , Animais , Região Hipotalâmica Lateral/citologia , Masculino , Microdiálise , Neurônios/fisiologia , Ratos , Ratos Sprague-Dawley , Água , Privação de Água/fisiologiaRESUMO
The effects of i.p. clozapine [0 (n = 6), 5 (n = 5), 10 (n = 5), 20 (n = 9) and 40 (n = 5) mg/kg] on acetylcholine (ACh) release in the prefrontal cortex (PFC), nucleus accumbens (NAC) and striatum (STR) were studied by simultaneous triple microdialysis in freely moving rats. Clozapine dose-responsively increased extracellular ACh in the studied areas. The effect was larger in the PFC. Comparisons of the slopes of the regression equations showed differences between the effects in PFC and nucleus accumbens (t = 4.29; df = 56; P < .001) and PFC and STR (t = 4.56), but not between nucleus accumbens and STR. These differential actions were not artifacts of the simultaneous perfusion because clozapine (20 mg/kg) increased ACh levels during single microdialysis of the PFC (353 +/- 72%; n = 5) or STR (168 +/- 24%; n = 5), in the same proportion as the respective increases in those areas during the simultaneous triple microdialysis (PFC = 330 +/- 41%; STR = 144 +/- 18%; n = 9). Local infusion of tetrodotoxin (10 microM) reduced ACh in the areas studied to about 30% of the mean baselines, confirming the neuronal origin of this neurotransmitter. Extrapolation of these results to humans suggests that adequate levels of cholinergic activity in the PFC are required for mental health, and that a similar ACh release in the human PFC by clozapine could be therapeutic. The low impact on striatal ACh could explain the lack of extrapyramidal symptoms by clozapine.
Assuntos
Acetilcolina/metabolismo , Antipsicóticos/farmacologia , Clozapina/farmacologia , Corpo Estriado/efeitos dos fármacos , Núcleo Accumbens/efeitos dos fármacos , Córtex Pré-Frontal/efeitos dos fármacos , Animais , Corpo Estriado/metabolismo , Masculino , Microdiálise , Núcleo Accumbens/metabolismo , Córtex Pré-Frontal/metabolismo , Ratos , Ratos Wistar , Tetrodotoxina/farmacologiaRESUMO
Drinking, feeding and hypothalamic extracellular acetylcholine (ACh) release was measured before and after the administration of several doses of atropine sulfate in streptozotocin (STZ)-diabetic and normal rats. Drinking but not feeding was dose-relatedly decreased by i.p. or intrahypothalamic injections of atropine in STZ-diabetic rats. Hypothalamic ACh release, as measured by microdialysis, increased less (dose-related) in diabetic than normal rats following an i.p. administration of atropine. Ach basal levels were the same in both groups. These results are discussed in terms of a hyperactive hypothalamic cholinergic (muscarinic) system involved in the diabetic polydipsia.
Assuntos
Acetilcolina/metabolismo , Atropina/farmacologia , Diabetes Mellitus Experimental/metabolismo , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Hipotálamo/metabolismo , Antagonistas Muscarínicos/farmacologia , Animais , Relação Dose-Resposta a Droga , Hipotálamo/efeitos dos fármacos , Injeções , Injeções Intraperitoneais , Masculino , Microdiálise , Ratos , Ratos Wistar , Valores de ReferênciaRESUMO
Mesolimbic dopamine (DA) was measured by ventral striatum (including nucleus accumbens) microdialysis in freely moving streptozotocin (STZ)-diabetic male rats. DA and dihydroxyphenylacetic acid (DOPAC) basal levels and amphetamine-induced DA increase were lower in diabetic than in normal rats. These results are discussed in terms of decreased DA neuron activity and DA receptor hypersensitivity in the mesolimbic system of STZ-diabetic rats.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Dopamina/metabolismo , Espaço Extracelular/metabolismo , Sistema Límbico/metabolismo , Ácido 3,4-Di-Hidroxifenilacético/metabolismo , Anfetamina/farmacologia , Animais , Cromatografia Líquida de Alta Pressão , Dopaminérgicos/farmacologia , Eletroquímica , Masculino , Microdiálise , Neostriado/efeitos dos fármacos , Neostriado/metabolismo , Ratos , Ratos WistarRESUMO
PACAP38 bilaterally injected in the vicinity of the perifornical lateral hypothalamus (pfLH) induced drinking behavior in rats. The animals (n = 12) drank 19.7 +/- 4.1 ml of water during the hour following PACAP38 microinjections (1 nmol/0.5 microliter). In the same rat sulpiride microinjections (45 nmol/0.5 microliter) had relatively mild effects (7.8 +/- 1.4 ml/h). The dipsogenic effects of sulpiride and PACAP38 were well correlated suggesting that both substances trigger drinking behavior activating the same hypothalamic mechanisms. Neither sulpiride nor PACAP38 promoted drinking when injected just 1.3 mm behind the effective zone. This negative result is an evidence of the neuroanatomical specificity of the dipsogenic effects of both substances. These preliminary results suggest that PACAP38 in the pfLH could be a neuropeptide regulating drinking behavior and perhaps body fluid volume and osmolarity and arterial blood pressure.
Assuntos
Comportamento de Ingestão de Líquido/efeitos dos fármacos , Hipotálamo Médio/fisiologia , Neuropeptídeos/farmacologia , Neurotransmissores/farmacologia , Animais , Antagonistas de Dopamina/farmacologia , Masculino , Microinjeções , Neuropeptídeos/administração & dosagem , Neurotransmissores/administração & dosagem , Polipeptídeo Hipofisário Ativador de Adenilato Ciclase , Ratos , Ratos Wistar , Análise de Regressão , Sulpirida/farmacologiaRESUMO
A low-torque, bubble-free and multiple-channel fluid swivel of easy construction was recently described. This paper describes the design, construction and testing of 3 electrical channels added to the original fluid swivel. The new channels were tested monitoring intrahypothalamic temperature (T(hy)) by means of a copper-constantan thermocouple in freely moving rats, before and after a single intraperitoneal (i.p.) amphetamine injection (3 mg/kg). This test showed an increase in T(hy) after the injection and the maintenance of the electrical continuity along the whole testing period, even when the animals were hyperactive. With this improvement the original swivel was transformed in a more versatile device for experiments requiring fluid handlings and electrophysiological manipulations. Electrical stimulation as in kindling or brain self-stimulation, and electrophysiological recordings as in electroencephalography, electromiography, electrocardiography, in vivo voltammetry and even neuronal unit recording, are just examples of the electrophysiological methods that can be combined with drug self-administration and microdialysis using the present device.
Assuntos
Encéfalo/fisiologia , Termografia/instrumentação , Animais , Temperatura Corporal/fisiologia , Estimulação Elétrica/instrumentação , Hipotálamo/fisiologia , Microinjeções , Modelos Neurológicos , Potenciometria , Ratos , Rotação , SoluçõesRESUMO
We studied the changes in airway mucus rheology and clearability, as well as in morphometric indices, between male rats and females in either the oestrous or dioestrous phases of the oestrous cycle. Three-month-old Wistar rats were studied and the phases of the oestrous cycle were determined based on analysis of vaginal smears stained by a modified Shorr's procedure. Nasal mucus samples were analysed by means of magnetic rheometry and determination of in vitro transport rate in the frog palate preparation. In situ clearance on the exposed nasal septum was also determined. The mucociliary velocity in situ was significantly affected by both sex and the oestrous cycle phase. In female rats, dioestrous phase clearance was significantly slower than the oestrous phase one. Clearance in male rats was faster than that of both the phases studied in females. Mucus rigidity of females in the oestrous phase was more rigid than that of females in the dioestrous phase and that of males. Mucus viscosity/elasticity ratio for deformations performed at high frequencies was greater for females in comparison with males. Cough clearability computed on the basis of rheological parameters was predicted to be more favourable in females. There were no significant differences between the three groups in mucociliary clearance in vitro. Morphometric studies of the nasal epithelium showed that epithelial and glandular volumes did not exhibit sex- or oestrous-phase-related differences, but the amount of epithelial acidic glycoproteins was lower in females in the oestrous phase in comparison with males and those in the dioestrous phase, the same trend being observed in the glands of the lamina propria.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Estro/fisiologia , Depuração Mucociliar/fisiologia , Muco/fisiologia , Mucosa Nasal/fisiologia , Caracteres Sexuais , Animais , Elasticidade , Feminino , Glicoproteínas/análise , Mucosa/citologia , Mucosa Nasal/química , Septo Nasal/anatomia & histologia , Ratos , Ratos Wistar , ReologiaRESUMO
Sulpiride in the perifornical lateral hypothalamus (pfLH) (4, 8 and 16 micrograms/0.5 microliter) increased intracranial temperature (Tic). The hyperthermia started immediately after the injection, peaked 30 min later and lasted for more than 90 min. Sulpiride (12 micrograms) accelerated recovery from hypothermia in anesthetized animals. Forty-five min after sulpiride Tic raised 1.17 +/- 0.06 degrees C. After a control injection the raise was only 0.5 +/- 0.13 degrees C. Locally applied dopamine (DA) (5, 10 and 20 micrograms) 5 min before sulpiride (12 micrograms) attenuated sulpiride hyperthermia. The largest DA dose reduced Tic (-1.21 degrees C) when administered alone. These findings suggest the existence of D2 receptors in the LH involved in thermoregulation. Changes are that D2 receptors in the human LH could be responsible for the neuroleptic malignant syndrome (NMS), and that sulpiride injections in the rat LH could be used as a model for the study of the pathogenesis of this syndrome.
Assuntos
Temperatura Corporal/efeitos dos fármacos , Encéfalo/efeitos dos fármacos , Dopamina/farmacologia , Região Hipotalâmica Lateral/fisiologia , Síndrome Maligna Neuroléptica/fisiopatologia , Sulpirida/farmacologia , Animais , Modelos Animais de Doenças , Febre/induzido quimicamente , Hipotermia/induzido quimicamente , Injeções , Masculino , Ratos , Ratos WistarRESUMO
This paper describes a new low-torque, bubble-free and multiple-channel swivel of easy construction. This swivel combined with the use of fused silica capillary tubing to connect syringes and injectors, as we recently proposed, allow the accurate and repeated microinjection of low nanoliter volumes (10 nl) in freely moving rats, as required in the intracranial self-administration paradigm. Microinjections can be simultaneously performed in 3 different brain regions. Relatively large volumes in the 10-100 microliters range can be repeatedly administered, as in intravenous self-administration, using the traditional connections with polyethylene (PE) tubing. This swivel allows the execution of experiments involving in vivo microdialysis in up to 3 different brain areas. The internal channel has a very low dead space (4 microliters) and can be used to withdraw small liquid samples and perform on-line microdialysis in freely moving animals. This versatility makes the present swivel appropriate for sophisticated experimental designs involving combinations of intracranial, intravenous and/or intragastric self-administration with microdialysis.
Assuntos
Injeções Intravenosas/instrumentação , Injeções/instrumentação , Microdiálise/instrumentação , Autoadministração/instrumentação , Animais , Encéfalo , Desenho de Equipamento , Equipamentos e Provisões , Estudos de Avaliação como Assunto , Cloreto de Sódio/administração & dosagemRESUMO
This report describes two improvements to the typical double-cannula microinjection technique. (1) Intracerebral microinjections usually require holding the animal during the insertion of an injector through an implanted guide cannula; however, this is not necessary with the technique described. The injector is made of a long piece of fused silica capillary tubing (145 mm outer diameter x 21.2 cm) which is so small and flexible that it slips through a PE-20 tube (20 cm) that guides it into the implanted guide cannula and down to the desired brain site where it stops. (2) Connection to a microliter syringe is usually done with PE tubing which is leaky, expandable and represents a relatively large dead space that makes it difficult to deliver small, accurate volumes. This problem is avoided by making connection to the syringe via another piece of silica glass capillary tubing. Thus both the injector and its connection to the syringe are made of glass. With these modifications the injector can be inserted without touching the animal, and accurate volumes in the low nanoliter range can be delivered.
Assuntos
Encéfalo/efeitos dos fármacos , Microinjeções/instrumentação , Animais , Microinjeções/métodos , Técnicas Estereotáxicas , VigíliaRESUMO
Although for many years it has been proposed that megadoses of pyridoxine protect from ethanol toxicity, this issue remains unclear. In the present report the interaction between ethanol and pyridoxine was tested. Pyridoxine was administered intramuscularly or intracerebroventricularly to rats. Intramuscular administration of 187.2 mg/kg of pyridoxine displaced the ethanol-lethality dose curve significantly toward the right (p < 0.005) and increased the LD50 of ethanol from 4.46 to 5.19 g/kg (p < 0.005). Intracerebroventricular administration of pyridoxine (1.1 mg) completely suppressed the mortality due to a LD100 of ethanol and the effect was dose dependent. We conclude that pyridoxine is an effective treatment for ethanol intoxication. The results are discussed in terms of an interaction of ethanol and pyridoxine on the GABAergic system.
Assuntos
Encéfalo/efeitos dos fármacos , Etanol/toxicidade , Piridoxina/farmacologia , Animais , Encéfalo/metabolismo , Feminino , Dose Letal Mediana , Ratos , Ratos Wistar , Ácido gama-Aminobutírico/metabolismoRESUMO
Dynamic viscoelasticity measurements are required in many studies on biological fluids and they can be performed by determining the corresponding strain when a sinusoidal shear stress is applied to a sample. In several circumstances the amount of fluid that can be obtained for analysis in physiological conditions does not exceed microliters. In this context, the microrheometer technique is a useful approach to determine the dynamic rheological profile of the samples. However, the manual calculation of the desired parameters is tedious and time-consuming. This paper describes a menu-oriented program in order to facilitate its use by non-experts. The comparison between manual and computer-aided calculations demonstrated that the program reduced the time of measurement, and reduced intra- and interobserver variations. The program was developed on an IBM compatible PC in Microsoft C 5.1, and tested in a blind study to check the advantages in terms of time and reproducibility of the system verified by the concordance of two independent observers (interobserver influence) in two different occasions (intraobserver influence).
Assuntos
Brônquios , Diagnóstico por Computador/normas , Magnetismo , Muco/fisiologia , Reologia , Validação de Programas de Computador , Elasticidade , Estudos de Avaliação como Assunto , Humanos , Modelos Lineares , Microcomputadores , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Processamento de Sinais Assistido por Computador , ViscosidadeRESUMO
Amphetamine (AMPH) injections into the lateral hypothalamus (LH) are known to inhibit feeding and this effect has been shown to be mediated by the release and the reuptake blockade of catecholamines. LH serotonin (5-HT) has been suggested to be involved in feeding inhibition and a recent study showed that LH amphetamine infusion increases extracellular dopamine (DA), norepinephrine (NE) and 5-HT, which suggests that 5-HT might also be involved in amphetamine anorexia. The present study investigated this possibility. A correlational study was performed between the anorectic effect of LH unilateral microinjections of each monoamine and the anorectic effect of AMPH. Six groups of male rats were used. The rats in each group were submitted to 2 series of 6 experimental sessions. Each session consisted of one microinjection in 24 h food-deprived rats, followed by the measurement of food intake 30 min later. The first series was similar for all groups and explored the AMPH effect (difference between the mean food intake after 3 AMPH injections (40 micrograms/0.5 microliter) and the mean food intake after 3 saline injections (0.5 microliter)). The second series explored the effects of DA (40 micrograms), NE (25 micrograms), EPI (25 micrograms), 5-HT (25 micrograms) or AMPH again, in a similar way as described for AMPH in the first series. Linear regression analysis on the first series AMPH effect and the amine effect of the 2nd series showed a positive correlation between both series of AMPH, AMPH and DA, and AMPH and 5-HT. This last correlation was replicated in a different group. No correlation was found between AMPH and NE or AMPH and epinephrine (EPI).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Anfetamina/administração & dosagem , Anorexia/fisiopatologia , Serotonina/fisiologia , Animais , Anorexia/induzido quimicamente , Epinefrina/fisiologia , Região Hipotalâmica Lateral , Injeções , Masculino , Norepinefrina/fisiologia , Ratos , Análise de RegressãoRESUMO
In order to assess the adverse effects of urban levels of air pollution, rats were used as biological indicators in a chronic exposure experiment. Animals were housed for 6 months in the center of São Paulo (the largest South American city) and were compared to controls kept for the same period in a clean area. Pollution levels were obtained from a State air pollution monitoring station, 200 m distant from the exposure place, which provided the levels of CO, SO2, particulates, and ozone. The animals were submitted to several tests focusing on the respiratory system, comprising pulmonary function tests, studies on mucociliary clearance and mucus rheology, histochemical evaluation of airways, bronchoalveolar lavage, and ultrastructural studies of the epithelium of the airways. Rats exposed to air pollution developed secretory cell hyperplasia in the airways, ultrastructural ciliary alterations, and a more rigid mucus, changes that caused mucociliary clearance impairment. In addition, nasal resistance and the number of inflammatory cells recovered by bronchoalveolar lavage were increased in air pollution exposed animals. The results obtained in the present investigation suggest that chronic exposure to urban levels of air pollution may cause respiratory lesions in rats.
Assuntos
Poluição do Ar/efeitos adversos , Pneumonia/etiologia , Sistema Respiratório/fisiopatologia , Saúde da População Urbana , Resistência das Vias Respiratórias , Animais , Brasil , Líquido da Lavagem Broncoalveolar , Cílios/ultraestrutura , Epitélio/patologia , Epitélio/ultraestrutura , Pulmão/patologia , Pulmão/ultraestrutura , Masculino , Microscopia Eletrônica , Depuração Mucociliar , Pneumonia/mortalidade , Ratos , Ratos Endogâmicos , Sistema Respiratório/patologia , Sistema Respiratório/ultraestrutura , Reologia , Saúde da População Rural , Emissões de Veículos/efeitos adversosRESUMO
Two experiments were conducted in order to see if dopamine satiety receptors in the lateral hypothalamus or satiety mechanisms in the ventromedial hypothalamus were involved in the hyperphagia and body weight increase induced by systemic sulpiride. In the first experiment, it was shown that systemic sulpiride (20 mg/kg) does not block the anorexia caused by intraperifornical injections of amphetamine. In the second experiment, sulpiride (20 mg/kg during 18 days) did not produce an additional increase in body weight in previously VMH-lesioned female rats. This last fact cannot be explained by a ceiling effect since insulin (5 U/day during 7 days) increased body weight in the same VMH rats in which sulpiride was not effective. These results do not support the hypothesis that systemic sulpiride reaches the perifornical dopamine D2 receptors to disinhibit feeding, but suggest instead an involvement of the ventromedial hypothalamus. This last suggestion is more in agreement with the hypothesis that sulpiride alters feeding and body weight gain through the induction of a functional gonadectomy.