RESUMO
We report on the first observation of γ rays emitted from an sd-shell hypernucleus, _{Λ}^{19}F. The energy spacing between the ground state doublet, 1/2^{+} and 3/2^{+} states, of _{Λ}^{19}F is determined to be 315.5±0.4(stat)_{-0.5}^{+0.6}(syst) keV by measuring the γ-ray energy of the M1(3/2^{+}â1/2^{+}) transition. In addition, three γ-ray peaks are observed and assigned as E2(5/2^{+}â1/2^{+}), E1(1/2^{-}â1/2^{+}), and E1(1/2^{-}â3/2^{+}) transitions. The excitation energies of the 5/2^{+} and 1/2^{-} states are determined to be 895.2±0.3(stat)±0.5(syst) and 1265.6±1.2(stat)_{-0.5}^{+0.7}(syst) keV, respectively. It is found that the ground state doublet spacing is well described by theoretical models based on existing s- and p-shell hypernuclear data.
RESUMO
Data related to radioactivity released from the Fukushima Daiichi Nuclear Power Plant (FDNPP) accident on 15 March 2011 gathered by residents of Miharu, Fukushima Prefecture, and by Tohoku University are presented. These data sets consist of (1) the earliest radiation monitoring by a Geiger counter in the town, (2) ratios of radioactivity between (132)Te and (137)Cs for a wide area between Fukushima and Tokyo, (3) radiation measurement of soil samples collected from 18 school grounds, and (4) external radiation exposure of 1400 students using OSL badges. By combining and analysing these various data sets, a curve for the cumulative total external exposure as a function of time, with 16 : 00 h on 15 March 2011 being time zero, is obtained. The average cumulative external dosage is estimated to be 10 mSv (σ = 4.2 mSv) over 10 years. In addition, the initiative that the residents of Miharu took in response to the FDNPP accident, which became known as The Misho Project (MP), is documented; in particular, the time at which the municipality instructed the immediate ingestion of iodine tablets by those under the age of 40, 13 : 00 h on 15 March 2011, is assessed.
Assuntos
Acidente Nuclear de Fukushima , Centrais Nucleares , Radiação Ionizante , Radiometria/estatística & dados numéricos , JapãoRESUMO
Absence seizures are a type of generalized onset seizure associated in humans with brief activity interruptions, unresponsiveness and staring. Absence seizures are infrequently reported in veterinary patients, visually indistinguishable from focal seizures, and so may be grouped as non-generalized tonic clonic seizures (non-GTCS). The objective of this retrospective study was to provide a preliminary understanding of the frequency of non-GTCS in dogs and estimate its prevalence by evaluating the distribution of seizure types presented to a referral hospital over 4 years (May 2017-April 2021), as determined from the medical record history and electroencephalography (EEG) diagnostic testing where available. A total of 528 cases were included via a medical record search for dogs with epilepsy and/or seizures presented to the neurology or emergency services. Cases were categorized into seizure types based on reported clinical signs. Each year, 53-63 % of seizure cases were described as generalized tonic clonic seizures (GTCS), 9-15 % GTCS with additional events and 29-35 % suspected non-GTCS. EEG confirmed absence seizures in 12 of 44 EEGs, 5 cases having a history of GTCS and seven without prior GTCS. This preliminary study suggests that non-GTCS may be relatively common as one third of seizure cases in the referral population presented with non-GTCS clinical signs. Prospective studies using EEG are merited to definitively determine the prevalence of these different seizure types in dogs. Acknowledging the impact of these seizures will improve awareness, aiding veterinarians in their recognition, diagnosis and potential treatment options.
Assuntos
Doenças do Cão , Epilepsia Tônico-Clônica , Epilepsia , Humanos , Cães , Animais , Epilepsia Tônico-Clônica/diagnóstico , Epilepsia Tônico-Clônica/tratamento farmacológico , Epilepsia Tônico-Clônica/veterinária , Estudos Retrospectivos , Estudos Prospectivos , Convulsões/diagnóstico , Convulsões/epidemiologia , Convulsões/veterinária , Epilepsia/diagnóstico , Epilepsia/epidemiologia , Epilepsia/veterinária , Eletroencefalografia/veterinária , Doenças do Cão/diagnóstico , Doenças do Cão/epidemiologiaRESUMO
The mechanism of DNA modification induced by K-shell photoabsorption of nitrogen and oxygen atoms was investigated by electron paramagnetic resonance and x-ray absorption near edge structure measurements of calf thymus DNA. A g factor of 2.000 for the unpaired electron species, which only arises during irradiation, was measured. The EPR intensities for DNA zwere twofold times larger than those estimated based on the photoabsorption cross section. This suggests that the DNA film itself forms unpaired electron species through the excitation of enhanced electron recapturing, known as the postcollision interaction process.
Assuntos
DNA/química , Elétrons , Nitrogênio/química , Oxigênio/química , Absorção , Animais , Bovinos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Processos FotoquímicosRESUMO
To identify the precise molecular processes to induce DNA lesions, we attempt a novel spectroscopy of X-ray induced luminescence (XIL) using soft X-ray synchrotron radiation, which is a non-destructive analysis of the reaction intermediates in the elementary reaction pathway of damage induction and self-organized restoration. Using a liquid micro-jet technique to introduce aqueous samples in a vacuum chamber, we measure UV-visible luminescence from nucleotide solution as a function of the soft X-ray energy from the nitrogen to oxygen K-edge region. The XIL intensities for the nucleotide solutions are significantly enhanced in the soft X-ray region (410-530 eV) which is ascribed to the K-shell excitation/ionization of nitrogen atoms in the nucleobases. Furthermore, the XIL spectra do not show any signature of X-ray absorption near-edge structure (XANES) of the nucleobases. This is because the luminescence intensities collected from the integral area of the micro-jet only reflect the quantum yield of luminescence of the absorbed X-ray into UV-visible light irrespective of the absorption cross sections, i.e. of XANES. Thus the present result is the first evidence of luminescence as a result of X-ray absorption of aqueous nucleotides.
Assuntos
DNA/química , DNA/efeitos da radiação , Desoxirribonucleotídeos/química , Desoxirribonucleotídeos/efeitos da radiação , Desenho de Equipamento , Concentração de Íons de Hidrogênio , Luminescência , Nitrogênio/química , Oxigênio/química , Síncrotrons , Água/química , Espectroscopia por Absorção de Raios XRESUMO
We generated transgenic mice expressing chimeric receptors, which comprise extracellular domains of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor and transmembrane and cytoplasmic domains of the mouse leukemia inhibitory factor receptor. In suspension cultures of lineage-negative (Lin(-)), 5-fluorouracil-resistant bone marrow cells of the transgenic mice, a combination of hGM-CSF and stem cell factor (SCF) induced exponential expansions of mixed colony-forming unit. The combination of hGM-CSF and SCF was effective on enriched, Lin(-)Sca-1(+)c-kit(+) progenitors and increased either mixed colony-forming unit or cobblestone area-forming cells. In case of stimulation with hGM-CSF and SCF, interleukin-6 (IL-6) and SCF, or IL-11 and SCF, the most efficient expansion was achieved with hGM-CSF and SCF. When Lin(-)Sca-1(+)c-kit(+)CD34(-) further enriched progenitors were clone sorted and individually incubated in the presence of SCF, hGM-CSF stimulated a larger number of cells than did IL-6, IL-6 and soluble IL-6 receptor (IL-6R), or IL-11. These data suggest the presence of IL-6Ralpha-, IL-11Ralpha-, and gp130-low to -negative primitive hematopoietic progenitors. Such primitive progenitors are equipped with signal transduction molecules and can expand when these chimeric receptors are genetically introduced into the cells and stimulated with hGM-CSF in the presence of SCF.
Assuntos
Antígenos CD/metabolismo , Inibidores do Crescimento , Células-Tronco Hematopoéticas/metabolismo , Interleucina-6 , Linfocinas , Glicoproteínas de Membrana/metabolismo , Receptores de Citocinas/metabolismo , Receptores de Interleucina-6/metabolismo , Receptores de Interleucina/metabolismo , Animais , Células Clonais , Ensaio de Unidades Formadoras de Colônias , Receptor gp130 de Citocina , Citometria de Fluxo , Fluoruracila/farmacologia , Fator Estimulador de Colônias de Granulócitos e Macrófagos/farmacologia , Humanos , Subunidade alfa de Receptor de Interleucina-11 , Fator Inibidor de Leucemia , Subunidade alfa de Receptor de Fator Inibidor de Leucemia , Camundongos , Camundongos Transgênicos , Receptores de Citocinas/genética , Receptores de Fator Estimulador das Colônias de Granulócitos e Macrófagos/genética , Receptores de Interleucina-11 , Receptores de OSM-LIF , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismoRESUMO
The present study was carried out to determine the involvement of dopamine receptor subtypes D3 and D4, in the discriminative stimulus effects of cocaine in the rats trained to discriminate 10 mg/kg of cocaine from vehicle. The discriminative stimulus effects of cocaine (1-10 mg/kg) were dose-dependent. The dopamine D2 receptor agonist bromocriptine (1.25-20 mg/kg) and the dopamine D3 receptor agonist R(+)-7-OH-DPAT (0.0001-0.3 mg/kg) produced cocaine (10 mg/kg)-like discriminative stimulus effects. Both the dopamine D3 receptor antagonist GR103691 (1 mg/kg) and the dopamine D4 receptor antagonist L745870 (1 mg/kg) partially antagonized the discriminative stimulus effects of cocaine (10 mg/kg) and the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). L745870 (0.001 mg/kg) inhibited the antagonistic effects of GR103691 (1 mg/kg) on the discriminative stimulus effects of cocaine (10 mg/kg), whereas the drug (0.001 mg/kg) enhanced the antagonistic effects of GR103691 (1 mg/kg) on the cocaine (10 mg/kg)-like discriminative stimulus effects of R(+)-7-OH-DPAT (0.3 mg/kg). GR103691 (1 mg/kg) in combination with L745870 (0.001 mg/kg) did not markedly affect the cocaine (10 mg/kg)-like discriminative stimulus effects of bromocriptine (20 mg/kg). These results suggest that the discriminative stimulus effects of cocaine are different from the cocaine-like discriminative stimulus effects of bromocriptine or R(+)-7-OH-DPAT, in terms of dopamine D3 and D4 receptors.
Assuntos
Bromocriptina/farmacologia , Cocaína/farmacologia , Discriminação Psicológica/efeitos dos fármacos , Agonistas de Dopamina/farmacologia , Inibidores da Captação de Dopamina/farmacologia , Tetra-Hidronaftalenos/farmacologia , Animais , Compostos de Bifenilo/farmacologia , Masculino , Piperazinas/farmacologia , Piridinas/farmacologia , Pirróis/farmacologia , Ratos , Ratos Endogâmicos F344 , Receptores de Dopamina D3/antagonistas & inibidores , Receptores de Dopamina D4/antagonistas & inibidoresRESUMO
Administration of neurotensin to dogs resulted in rises in circulating blood glucose, glucagon and insulin levels, the rise in glucagon being more pronounced than that in insulin. Infusion of somatostatin along with neurotensin suppressed glucagon and insulin responses to neurotensin and prevented the rise in blood glucose levels. These results suggest that the hyperglycemia seen after neurotensin is due to neurotensin stimulation of glucagon release over insulin release.
Assuntos
Glicemia/metabolismo , Glucagon/sangue , Proteínas do Tecido Nervoso/farmacologia , Somatostatina/farmacologia , Animais , Cães , Feminino , Veias Hepáticas , Hipotálamo , Insulina/sangue , Veia PortaRESUMO
The effects of intracerebral injection of dynorphin-(1-13) on spontaneous locomotor activity were investigated by using a newly devised multi-dimensional behavioural analyser based on a capacitance system. With this equipment, nine different measures of behavior exhibited by the mouse can be recorded. It was found that dynorphin-(1-13) (0.3 and 1 microgram) produced a significant increase in the linear locomotion recorded on the 1/1 and 1/2 counters. In addition, dynorphin-(1-13) (0.3 micrograms) significantly increased the grooming behavior recorded on the 1/16 counter. As the dynorphin-(1-13)-induced behavioural effects were reversed by pretreatment with relatively small doses of naloxone (0.5, 1 and 2 mg/kg), the dynorphin-induced increases in linear locomotion and grooming are probably mediated through opiate receptors in the brain.
Assuntos
Dinorfinas , Endorfinas/farmacologia , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Fragmentos de Peptídeos/farmacologia , Animais , Relação Dose-Resposta a Droga , Endorfinas/antagonistas & inibidores , Masculino , Camundongos , Fragmentos de Peptídeos/antagonistas & inibidores , Fatores de TempoRESUMO
The present study examined the effects of intracerebroventricular injection of dynorphin A-(1-13) on memory processes by using the passive avoidance task in mice. Galanin (0.3 microgram) significantly shortened the step-down latency when given 15 min before retention tests. Although dynorphin A-(1-13) (1 or 3 micrograms) did not prolong the step-down latency induced by weaker electroshocks, it inhibited the galanin (0.3 micrograms)-induced shortening of step-down latency. The effects of dynorphin A-(1-13) (3 micrograms) on the galanin-induced shortening of step-down latency were almost completely reversed by pretreatment with nor-binaltorphimine (4 micrograms), a kappa-selective opioid antagonist. These results strongly suggest that dynorphin A-(1-13) attenuates galanin-induced impairment of memory processes through the mediation of kappa-opioid receptors.
Assuntos
Dinorfinas/farmacologia , Memória/efeitos dos fármacos , Fragmentos de Peptídeos/farmacologia , Peptídeos/farmacologia , Amnésia/induzido quimicamente , Animais , Galanina , Masculino , Camundongos , Receptores Opioides kappa/efeitos dos fármacosRESUMO
The effects of the opioid antagonist, Mr2266 [(-)-(1R,5R,9R)-5,9-diethyl-2-(3-furyl-methyl)-2'-hydroxy-6,7-benzomo rph an] on the intake of water and saline (0.9%) were investigated in the mouse, deprived of water for 24 hr. In an attempt to evaluate motor functions, the behavior after treatment with Mr2266 was also examined by using multi-dimensional behavioral analyses. Although smaller doses (1.0, 3.0 and 10.0 mg/kg) of Mr2266 failed to affect significantly the intake of water, a larger dose (30.0 mg/kg) elicited a significant attenuation in the intake of water. During a 30 min observation, Mr2266 (30.0 mg/kg) depressed markedly linear locomotion, while other behavioral responses, such as rearing and grooming, remained unchanged. In contrast, 1.0-30.0 mg/kg doses of the drug produced a significant reduction in the intake of saline. The drug Mr2266 had no significant effects on the latency to start drinking at any doses tested. These results suggest that Mr2266 specifically blocks the intake of saline of the mouse through the mediation of opioid systems.
Assuntos
Benzomorfanos/farmacologia , Ingestão de Líquidos/efeitos dos fármacos , Morfinanos/farmacologia , Antagonistas de Entorpecentes/farmacologia , Cloreto de Sódio , Animais , Eletrodos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos , MicrocomputadoresRESUMO
The effects of intracerebroventricular injection of the delta-selective opioid peptides, DADL (D-Ala2-D-Leu5-enkephalin) and DPLPE (D-Pen2-L-Pen5-enkephalin), on spontaneous locomotor activity were investigated in mice using multi-dimensional behavioral analysis, based upon a capacitance system. The analysers classified the movements into 9 sizes (1/1, 1/2, 1/4, 1/8, 1/16, 1/32, 1/64, 1/128 and 1/256). Specific patterns of behavior were each registered on these sizes of movement. At 1.0 and 3.0 micrograms, DADL produced a significant increase in circling (1/4 size of movements) within 15 min after the start of measurements, while it produced a marked increase in linear locomotion (1/2 size), circling (1/4 size), rearing (1/16 size) and grooming (1/32, 1/64 and 1/128 sizes) within 15-30 min after the start. At 10.0 micrograms, DPLPE decreased linear locomotion (1/1 size) and conversely increased circling behavior (1/4 size) within 15 min after the start, whilst this peptide at 3.0 or 10.0 micrograms, produced a marked increase in linear locomotion (1/2 size), circling (1/4 size) and grooming (1/128 size) within 15-30 min after the start. The behavioral effects induced by DADL (3.0 micrograms) and DPLPE (10.0 micrograms) were completely reversed by naloxone (1.0 and 2.0 mg/kg). These results obtained with DPLPE, a delta-selective peptide and DADL, a less delta-selective peptide, indicate a common pattern of activity which was presumably delta receptor-mediated. However, one component (linear locomotion, at times immediately after administration of the peptide) did clearly differ between these two peptide analogues.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Comportamento Animal/efeitos dos fármacos , Encefalinas/farmacologia , Receptores Opioides/fisiologia , Animais , D-Penicilina (2,5)-Encefalina , Encefalina Leucina/antagonistas & inibidores , Encefalina Leucina/farmacologia , Leucina Encefalina-2-Alanina , Encefalinas/antagonistas & inibidores , Masculino , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Naloxona/farmacologia , Receptores Opioides/efeitos dos fármacos , Receptores Opioides deltaRESUMO
The effects of intracerebroventricular (i.c.v.) injections of mu- and delta-selective opioid agonists on the methamphetamine-induced behavioral alterations in the mouse were determined by using multi-dimensional behavioral analyses. Methamphetamine (1.0 mg/kg) produced a marked increase in linear locomotion, circling, rearing and grooming behavior. Although the mu-selective opioid agonist [D-Ala2,NMePhe4,Gly-ol]enkephalin (DAMGO) (0.003 and 0.01 microgram) itself did not significantly affect different behavioral responses, DAMGO (0.003 and/or 0.01 microgram) antagonized the methamphetamine (1.0 mg/kg)-induced increase in behavioral responses such as linear locomotion, circling, rearing and grooming. Additionally, the effects of DAMGO (0.01 microgram) on the methamphetamine (1.0 mg/kg)-induced behavioral responses were fully reversed by pretreatment with the mu-selective alkylating agent beta-funaltrexamine (beta-FNA) (5.0 micrograms). In contrast, the delta-selective opioid agonist [D-Pen2,L-Pen5]enkephalin (DPLPE) (0.3 or 1.0 microgram) had no marked effects on the methamphetamine (1.0 mg/kg)-induced behavioral responses. These results suggest that the stimulation of mu but not delta opioid receptors plays an inhibitory role in the methamphetamine-induced behavioral responses.
Assuntos
Analgésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Encefalinas/farmacologia , Metanfetamina/antagonistas & inibidores , Analgésicos/administração & dosagem , Animais , Ala(2)-MePhe(4)-Gly(5)-Encefalina , D-Penicilina (2,5)-Encefalina , Encefalinas/administração & dosagem , Injeções Intraventriculares , Masculino , Camundongos , Camundongos Endogâmicos , Naltrexona/análogos & derivados , Naltrexona/farmacologia , Antagonistas de Entorpecentes/farmacologiaRESUMO
The effects of systemic administration (i.p.) of dynorphin A(1-13) on the cocaine-induced behavioural alterations in the mouse were determined by using multi-dimensional behavioural analyses, based upon a capacitance system. A 1.0 mg/kg dose of cocaine did not influence behaviour, while increasing doses to 3-30 mg/kg produced a significant increment in the frequency of behaviour, such as linear locomotion, circling, rearing and grooming. Although a 1.0 mg/kg dose of dynorphin A(1-13) alone produced a significant decrease in grooming behaviour, larger doses (3.0 and 10.0 mg/kg) of the peptide failed to affect different behaviour. The cocaine (3.0 mg/kg)-induced increases in linear locomotion, circling and rearing behaviour were significantly inhibited by dynorphin A(1-13) (10.0 mg/kg). The inhibitory effects of dynorphin A(1-13) (10.0 mg/kg) were antagonized by the opioid antagonist Mr 2266 (5.6 mg/kg). It is thus possible that the systemic administration of dynorphin A(1-13) inhibits different behavioural responses induced by cocaine through the blood-brain barrier, although the instability of amino acid bonds or the relatively large molecular weight of dynorphin A(1-13), may result in the failure to demonstrate opioid activity by the peptide after systemic administration.
Assuntos
Analgésicos/farmacologia , Comportamento Animal/efeitos dos fármacos , Cocaína/farmacologia , Dinorfinas/farmacologia , Fragmentos de Peptídeos/farmacologia , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Animais , Benzomorfanos/farmacologia , Dinorfinas/administração & dosagem , Injeções Intraperitoneais , Masculino , Camundongos , Camundongos Endogâmicos , Atividade Motora/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Fragmentos de Peptídeos/administração & dosagemRESUMO
The effects of recombinant alpha-human atrial natriuretic peptide (alpha-hANP) infusion an acute left ventricular dysfunction provoked by exercise were examined in 14 men with coronary artery disease. Patients performed symptom-limited, graded exercise on a supine bicycle ergometer. Plasma alpha-hANP and guanosine 3',5'-monophosphate (cyclic GMP) concentrations as well as hemodynamic variables were measured at rest, during and after exercise. In 14 patients whose pulmonary artery wedge pressure was > 20 mm Hg at peak exercise, the same exercise protocol was repeated at 30 minutes after starting intravenous alpha-hANP infusion (0.05 microgram.kg-1.min-1). In 8 of these patients, a Webster thermodilution catheter was advanced into the coronary sinus for measurement of coronary sinus blood flow. From the control exercise test, plasma alpha-hANP concentration increased from 86 +/- 20 pg/ml at rest to 188 +/- 32 pg/ml at peak exercise (p < 0.001), and plasma cyclic GMP concentration increased from 4.8 +/- 1.9 pmol/ml at rest to 7.2 +/- 2.9 pmol/ml at peak exercise (p < 0.001). Both plasma alpha-hANP and cyclic GMP concentrations showed a significant positive correlation with pulmonary artery wedge pressure during control exercise. With alpha-hANP infusion, systolic and diastolic pulmonary artery pressures and pulmonary artery wedge pressure were significantly decreased at all time points during exercise testing. Heart rate was increased and systolic blood pressure was significantly decreased at rest and at 3 minutes of exercise. Diastolic blood pressure, systemic vascular resistance, and pulmonary vascular resistance were significantly decreased at rest.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Fator Natriurético Atrial/uso terapêutico , Doença das Coronárias/fisiopatologia , Disfunção Ventricular Esquerda/tratamento farmacológico , Idoso , Fator Natriurético Atrial/sangue , Fator Natriurético Atrial/farmacologia , Circulação Coronária/efeitos dos fármacos , Doença das Coronárias/sangue , Doença das Coronárias/complicações , GMP Cíclico/sangue , Teste de Esforço , Hemodinâmica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/sangue , Disfunção Ventricular Esquerda/complicações , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
Humanin is a very recently discovered 24 amino acid linear polypeptide, which protects against cell death induced by either familial Alzheimer's disease mutant of amyloid precursor protein, presenilin-1 or presenilin-2 in vitro. However, it has remained uncertain whether humanin is a useful drug for the animal model of learning and memory deficit. In this study, we evaluated the effects of [Gly(14)]-humanin, a more potent humanin analogue, on the scopolamine HBr (1 mg kg(-1) s.c.)-induced impairment of spontaneous alternation behaviour in the Y-maze, an index of short-term memory in mice. [Gly(14)]-Humanin (1000 pmol 5 microl(-1) i.c.v.) reversed the impairment without affecting the number of arm entries. These results suggest that (I) [Gly(14)]-humanin is a beneficial drug for the impairment of learning and memory and (II) it modulates the learning and memory function mediated via cholinergic systems in mice.
Assuntos
Deficiências da Aprendizagem/tratamento farmacológico , Transtornos da Memória/tratamento farmacológico , Antagonistas Muscarínicos/farmacologia , Fármacos Neuroprotetores/farmacologia , Peptídeos/farmacologia , Proteínas/farmacologia , Escopolamina/antagonistas & inibidores , Sequência de Aminoácidos , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Comportamento Animal/efeitos dos fármacos , Defecação/efeitos dos fármacos , Relação Dose-Resposta a Droga , Peptídeos e Proteínas de Sinalização Intracelular , Deficiências da Aprendizagem/induzido quimicamente , Aprendizagem em Labirinto/efeitos dos fármacos , Memória/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Mutantes , Dados de Sequência Molecular , Fatores de TempoRESUMO
The role of the different opioid receptors was studied in rats trained to discriminate SC injections of 3.0 mg/kg morphine from saline by tests for generalization to graded doses of morphine and receptor-selective peptides administered into the lateral cerebral ventricle. Dose-dependent morphine-like stimulus effects were produced over a wide range of doses (0.001-30 micrograms), depending upon ligand and animal, by morphine, by the mu-selective peptides DAGO[D-Ala2-NMePhe4-Gly(ol)-enkephalin] and FK33824[D-Ala2,NMePhe4-Met(O)5-(ol)-enkephalin], and by the delta-selective peptide, DADL[D-Ala2,D-Leu5)enkephalin]. The order of relative potency of these substances was: FK33824 greater than DAGO greater than morphine greater than DADL. In contrast, DPLPE[D-Pen2,L-Pen5)enkephalin], which has much greater delta receptor selectivity than does DADL, and dynorphin A(1-13) (0.1-10 micrograms), a kappa-receptor agonist, engendered choice responding appropriate for saline. When 1.0 micrograms DADL, a dose lacking morphine-like discriminative effects, was administered concurrently with SC morphine, the stimulus effects of morphine were potentiated. Concurrent administration of 10 micrograms dynorphin A(1-13) and morphine attenuated the stimulus effects of morphine inconsistently. These results support previous findings that mu-opioid receptors are of primary importance in mediating the morphine-like discriminative effects of opioid peptides. They also suggest that morphine-like discriminative effects can be modulated by other types of opioid receptors.
Assuntos
Discriminação Psicológica/efeitos dos fármacos , Dinorfinas/farmacologia , Encefalina Leucina/análogos & derivados , Morfina/farmacologia , Fragmentos de Peptídeos/farmacologia , Animais , Aprendizagem por Discriminação/efeitos dos fármacos , Interações Medicamentosas , Encefalina Leucina/farmacologia , Leucina Encefalina-2-Alanina , Injeções Intraventriculares , Injeções Subcutâneas , Masculino , Ratos , Receptores Opioides/fisiologia , Receptores Opioides delta , Receptores Opioides kappa , Receptores Opioides muRESUMO
The effects of naltrexone methobromide, a quaternary derivative of the opioid antagonist naltrexone, were investigated on deprivation (24 h)-induced water intake in the unilaterally cannulated rats. Naltrexone methobromide reduced post-deprivational water intake with an ED50 of 7.3 micrograms when tested at 30 min (peak effect) after intracerebroventricular administration. It also dose-dependently (0.3-10 micrograms) depressed water intake, with peak effects at 15 min, after microinjection into the paraventricular hypothalamic nucleus and into the supraoptic hypothalamic nucleus. The drug did not produce any other effects on behaviors. The ED50S were 1.4 micrograms when given into the paraventricular nucleus, and 3.3 micrograms when given into the supraoptic nucleus, respectively. Although injections of higher doses (1.0, 3.0 and/or 10 micrograms) of the drug into the preoptic area, zona incerta, and corpus callosum significantly suppressed water intake, other behavioral manifestations, such as rotational behaviors, convulsions, body shakes, head swaying, and/or backward locomotion were manifested simultaneously with the reduction in drinking. When injected into the lateral hypothalamic area, water intake was not significantly affected by the drug. These findings suggest that the paraventricular and supraoptic hypothalamic nuclei are important sites of action in the naltrexone-induced suppression of water intake.
Assuntos
Ingestão de Líquidos/efeitos dos fármacos , Antagonistas de Entorpecentes/farmacologia , Privação de Água , Animais , Hipotálamo/fisiologia , Injeções Intraventriculares , Masculino , Naltrexona/farmacologia , Ratos , Ratos EndogâmicosRESUMO
We examined whether dopamine D4 receptor is involved in morphine dependence in mice. Mice pretreated with morphine (10 mg/kg, s.c.) twice a day for 5 days showed withdrawal syndromes such as jumping, rearing, and forepaw tremors after the administration of naloxone (2 mg/kg, i.p.) on the sixth day. Such mice exhibited significant elevation of cAMP levels in the thalamus compared with the control mice. L-745,870 (1 mg/kg, i.p.), a selective dopamine D4 receptor antagonist, pretreated with morphine on the sixth day, significantly attenuated the severity of withdrawal syndromes and the increase in cAMP levels after the administration of naloxone. These results suggest that (1) the elevation of cAMP levels is involved in the expression of morphine-induced withdrawal syndromes, and (2) dopamine D4 receptor antagonists inhibit the expression of morphine-induced withdrawal syndromes accompanied with biochemical changes in mice. Furthermore, dopamine D4 receptor antagonists may be useful drugs for attenuating the expression of morphine dependence.
Assuntos
Antagonistas de Dopamina/uso terapêutico , Antagonistas dos Receptores de Dopamina D2 , Dependência de Morfina/tratamento farmacológico , Naloxona/farmacologia , Piridinas/uso terapêutico , Pirróis/uso terapêutico , Animais , AMP Cíclico/metabolismo , Antagonistas de Dopamina/farmacologia , Masculino , Camundongos , Dependência de Morfina/metabolismo , Piridinas/farmacologia , Pirróis/farmacologia , Receptores de Dopamina D2/metabolismo , Receptores de Dopamina D4 , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Síndrome de Abstinência a Substâncias/metabolismoRESUMO
The effects of intracerebroventricular injection of endomorphin-1 and 2, endogenous mu-opioid receptor agonists, on the scopolamine-induced impairment of spontaneous alternation performance associated with short-term memory were investigated in mice. Endomorphin-1 (0.03 microg) inhibited scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance without affecting total arm entries, while endomorphin-2 (0.01-10 microg) failed to significantly influence the scopolamine (1 mg/kg)-induced impairment. Endomorphin-1 (0.03 microg) itself had no marked effects on spontaneous alternation performance in intact mice. Although beta-funaltrexamine (5 microg), a mu-opioid receptor antagonist, did not significantly affect the inhibitory effects of endomorphin-1 (0.03 microg) on the scopolamine (1 mg/kg)-induced impairment, naloxonazine (35 mg/kg), a mu1-opioid receptor antagonist, significantly reversed the inhibitory effects of endomorphin-1 (0.03 microg) on the impairment. Naloxonazine (35 mg/kg) unlike beta-funaltrexamine (5 microg) did not significantly influence the scopolamine (1 mg/kg)-induced impairment of spontaneous alternation performance. These results suggest that endomorphin-1 improves the disturbance of short-term memory resulting from cholinergic dysfunction through the mediation of mu1-opioid receptors.