RESUMO
Fibromyalgia is characterized by the amplification of central nervous system pain with concomitant fatigue, sleep, mood disorders, depression, and anxiety. It needs extensive pharmacological therapy. In the present study, Swiss mice were treated with reserpine (0.25 mg/kg, s.c.) over three consecutive days, in order to reproduce the pathogenic process of fibromyalgia. On day 4, the administrations of the Tx3-3 toxin produced significant antinociception in the mechanical allodynia (87.16% ±12.7%) and thermal hyperalgesia (49.46% ± 10.6%) tests when compared with the PBS group. The effects produced by the classical analgesics (duloxetine 30 mg/kg, pramipexole 1 mg/kg, and pregabalin 30 mg/kg, p.o., respectively) in both of the tests also demonstrated antinociception. The administrations were able to increase the levels of the biogenic amines (5-HTP and DE) in the brain. The treatments with pramipexole and pregabalin, but not duloxetine, decreased the immobility time in the FM-induced animals that were submitted to the forced swimming test; however, the Tx3-3 toxin (87.45% ± 4.3%) showed better results. Taken together, the data has provided novel evidence of the ability of the Tx3-3 toxin to reduce painful and depressive symptoms, indicating that it may have significant potential in the treatment of FM.
Assuntos
Analgésicos/administração & dosagem , Fibromialgia/tratamento farmacológico , Neuropeptídeos/administração & dosagem , Anestésicos/administração & dosagem , Animais , Modelos Animais de Doenças , Fibromialgia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Masculino , Camundongos , Reserpina/administração & dosagemRESUMO
AIMS: Immunization with neural-derived peptides (INDP) has demonstrated to be a promising therapy to achieve a regenerative effect in the chronic phase of the spinal cord injury (SCI). Nevertheless, INDP-induced neurogenic effects in the chronic stage of SCI have not been explored. METHODS AND RESULTS: In this study, we analyzed the effect of INDP on both motor and sensitive function recovery; afterward, we assessed neurogenesis and determined the production of cytokines (IL-4, IL-10, and TNF alpha) and neurotrophic factors (BDNF and GAP-43). During the chronic stage of SCI, rats subjected to INDP showed a significant increase in both motor and sensitive recovery when compared to the control group. Moreover, we found a significant increase in neurogenesis, mainly at the central canal and at both the dorsal and ventral horns of INDP-treated animals. Finally, INDP induced significant production of antiinflammatory and regeneration-associated proteins in the chronic stages of SCI. CONCLUSIONS: These findings suggest that INDP has a neurogenic effect that could improve motor and sensitive recovery in the chronic stage of SCI. Moreover, our results also envision the use of INDP as a possible therapeutic strategy for other trauma-related disorders like traumatic brain injury.
Assuntos
Imunização/métodos , Neurogênese/efeitos dos fármacos , Neuropeptídeos/administração & dosagem , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/terapia , Animais , Feminino , Mediadores da Inflamação/antagonistas & inibidores , Mediadores da Inflamação/metabolismo , Neurogênese/fisiologia , Medição da Dor/efeitos dos fármacos , Medição da Dor/métodos , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/imunologiaRESUMO
ABSTRACT Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise. Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 μg/rat), and dimethyl sulfoxide (DMSO). After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma). Our results suggest that all doses of irisin (0.5, 1, 1.5 μg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.
RESUMO A indução de potenciação de longo prazo (LTP) aumenta a capacidade de armazenamento das sinapses no giro denteado (DG) do hipocampo. A irisina é uma miocina gerada a partir do FNDC5 (um precursor genético) durante o exercício. Embora a administração intra-Cornu Ammonis1 de irisina fortaleça a LTP em camundongos com doença de Alzheimer, os efeitos da injeção intra-denteada de irisina sobre a LTP em ratos ainda precisam ser elucidados in vivo. Neste estudo, ratos Wistar machos foram divididos aleatoriamente em um grupo controle (solução salina), irisina (0,5, 1 e 1,5 μg / rato) e dimetilsulfóxido (DMSO). Após o tratamento, a amplitude do pico populacional (PS) e a variação dos potenciais pós-sinápticos excitatórios (EPSP) foram medidos no DG de ratos in vivo. Além disso, após a conclusão das experiências, os locais de estimulação e registro no hipocampo foram confirmados histologicamente a partir de secções do cérebro. Adicionalmente, ensaios bioquímicos como malondialdeído (MDA), capacidade antioxidante total (TAC) e status oxidante total (TOS) foram avaliados (os marcadores antioxidantes foram analisados no plasma). Nossos resultados sugerem que todas as doses de irisina (0,5, 1, 1,5 μg / rato) causaram um aumento na variação da EPSP e na amplitude da PS quando comparadas com o grupo controle. Além disso, os resultados obtidos mostraram que a irisina diminuiu os níveis de TOS e MDA, enquanto aumentou os níveis de TAC como um marcador da peroxidação lipídica no plasma. O presente estudo fornece evidências diretas de que a irisina afeta a plasticidade sináptica dependente de atividade no DG.
Assuntos
Animais , Masculino , Neuropeptídeos/administração & dosagem , Fibronectinas/administração & dosagem , Potenciação de Longa Duração/efeitos dos fármacos , Giro Denteado/efeitos dos fármacos , Microinjeções/métodos , Valores de Referência , Fatores de Tempo , Peroxidação de Lipídeos , Distribuição Aleatória , Reprodutibilidade dos Testes , Ratos Wistar , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Malondialdeído/sangue , Antioxidantes/análiseRESUMO
OBJECTIVE: Induction of long-term potentiation (LTP) increases the storage capacity of synapses in the hippocampal dentate gyrus (DG). Irisin is a myokine generated from FNDC5 (a gene precursor) during exercise. METHODS: Although intra-cornu ammonis 1 administration of irisin fortifies LTP in mice with Alzheimer's disease, the effects of intra-DG injection of irisin on the LTP in rats remains to be elucidated in vivo. In this study, male Wistar rats were randomly divided into a control group (saline), irisin (0.5, 1, and 1.5 µg/rat), and dimethyl sulfoxide (DMSO). RESULTS: After treatment, the population spike (PS) amplitude and slope of excitatory postsynaptic potentials (EPSP) were measured in the DG of rats in vivo. Moreover, following completion of the experiments, the stimulating and recording sites in the hippocampus were confirmed histologically from brain sections. Furthermore, biochemical assays like malondialdehyde (MDA), total antioxidant capacity (TAC), and total oxidant status (TOS) were evaluated (the antioxidant markers were analyzed in the plasma). CONCLUSION: Our results suggest that all doses of irisin (0.5, 1, 1.5 µg/rat) caused an increase in the EPSP slope and PS amplitude when compared with the control group. In addition, the results obtained showed that irisin decreased TOS and MDA levels while increasing TAC levels as a marker of lipid peroxidation in plasma. The present report provides direct evidence that irisin affects the activity-dependent synaptic plasticity in the dentate gyrus.
Assuntos
Giro Denteado/efeitos dos fármacos , Fibronectinas/administração & dosagem , Potenciação de Longa Duração/efeitos dos fármacos , Microinjeções/métodos , Neuropeptídeos/administração & dosagem , Animais , Antioxidantes/análise , Fator Neurotrófico Derivado do Encéfalo/análise , Fator Neurotrófico Derivado do Encéfalo/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Peroxidação de Lipídeos , Masculino , Malondialdeído/sangue , Distribuição Aleatória , Ratos Wistar , Valores de Referência , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
BACKGROUND: Immunization with neural derived peptides (INDP) as well as scar removal-separately-have shown to induce morphological and functional improvement after spinal cord injury (SCI). In the present study, we compared the effect of INDP alone versus INDP with scar removal on motor recovery, regeneration-associated and cytokine gene expression, and axonal regeneration after chronic SCI. Scar removal was conducted through a single incision with a double-bladed scalpel along the stump, and scar renewal was halted by adding α,α'-dipyridyl. RESULTS: During the chronic injury stage, two experiments were undertaken. The first experiment was aimed at testing the therapeutic effect of INDP combined with scar removal. Sixty days after therapeutic intervention, the expression of genes encoding for TNFα, IFNγ, IL4, TGFß, BDNF, IGF1, and GAP43 was evaluated at the site of injury. Tyrosine hydroxylase and 5-hydroxytryptamine positive fibers were also studied. Locomotor evaluations showed a significant recovery in the group treated with scar removal + INDP. Moreover; this group presented a significant increase in IL4, TGFß, BDNF, IGF1, and GAP43 expression, but a decrease of TNFα and IFNγ. Also, the spinal cord of animals receiving both treatments presented a significant increase of serotonergic and catecholaminergic fibers as compared to other the groups. The second experiment compared the results of the combined approach versus INDP alone. Rats receiving INDP likewise showed improved motor recovery, although on a lesser scale than those who received the combined treatment. An increase in inflammation and regeneration-associated gene expression, as well as in the percentage of serotonergic and catecholaminergic fibers was observed in INDP-treated rats to a lesser degree than those in the combined therapy group. CONCLUSIONS: These findings suggest that INDP, both alone and in combination with scar removal, could modify the non-permissive microenvironment prevailing at the chronic phase of SCI, providing the opportunity of improving motor recovery.
Assuntos
Cicatriz/metabolismo , Locomoção/efeitos dos fármacos , Neuropeptídeos/administração & dosagem , Traumatismos da Medula Espinal/imunologia , Traumatismos da Medula Espinal/metabolismo , Vacinação , Animais , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Doença Crônica , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Proteína GAP-43/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Interferon gama/metabolismo , Interleucina-4/metabolismo , Neuropeptídeos/uso terapêutico , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica , Traumatismos da Medula Espinal/tratamento farmacológico , Regeneração da Medula Espinal/genética , Fator de Crescimento Transformador beta/metabolismo , Fator de Necrose Tumoral alfa/metabolismoRESUMO
The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 μM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 μM) decreased MAP50, and SST (0.05 μM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.
Assuntos
Animais , Masculino , Pressão Arterial/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Complexo Nuclear Corticomedial/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Neuropeptídeos/farmacologia , Vigília , Análise de Variância , Angiotensina II/administração & dosagem , Encéfalo/anatomia & histologia , Sistema Cardiovascular/inervação , Complexo Nuclear Corticomedial/metabolismo , Hemodinâmica/efeitos dos fármacos , Microinjeções , Neuropeptídeos/administração & dosagem , Ocitocina/administração & dosagem , Sistema Nervoso Parassimpático/efeitos dos fármacos , Ratos Wistar , Estatísticas não Paramétricas , Somatostatina/administração & dosagem , Sistema Nervoso Simpático/efeitos dos fármacos , Dispositivos de Acesso VascularRESUMO
BACKGROUND AND PURPOSE: Spinal voltage-gated calcium channels (VGCCs) are pivotal regulators of painful and inflammatory alterations, representing attractive therapeutic targets. We examined the effects of epidural administration of the P/Q- and N-type VGCC blockers Tx3-3 and Phα1ß, respectively, isolated from the spider Phoneutria nigriventer, on symptomatic, inflammatory and functional changes allied to mouse cyclophosphamide (CPA)-induced haemorrhagic cystitis (HC). The effects of P. nigriventer-derived toxins were compared with those displayed by MVIIC and MVIIA, extracted from the cone snail Conus magus. EXPERIMENTAL APPROACH: HC was induced by a single i.p. injection of CPA (300 mg·kg(-1) ). Dose- and time-related effects of spinally administered P/Q and N-type VGCC blockers were assessed on nociceptive behaviour and macroscopic inflammation elicited by CPA. The effects of toxins were also evaluated on cell migration, cytokine production, oxidative stress, functional cystometry alterations and TRPV1, TRPA1 and NK1 receptor mRNA expression. KEY RESULTS: The spinal blockage of P/Q-type VGCC by Tx3-3 and MVIIC or N-type VGCC by Phα1ß attenuated nociceptive and inflammatory events associated with HC, including bladder oxidative stress and cytokine production. CPA produced a slight increase in bladder TRPV1 and TRPA1 mRNA expression, which was reversed by all the toxins tested. Noteworthy, Phα1ß strongly prevented bladder neutrophil migration, besides HC-related functional alterations, and its effects were potentiated by co-injecting the selective NK1 receptor antagonist CP-96345. CONCLUSIONS AND IMPLICATIONS: Our results shed new light on the role of spinal P/Q and N-type VGCC in bladder dysfunctions, pointing out Phα1ß as a promising alternative for treating complications associated with CPA-induced HC.
Assuntos
Bloqueadores dos Canais de Cálcio/farmacologia , Canais de Cálcio Tipo N/metabolismo , Cistite/tratamento farmacológico , Hemorragia/tratamento farmacológico , Neuropeptídeos/farmacologia , Venenos de Aranha/farmacologia , Animais , Bloqueadores dos Canais de Cálcio/administração & dosagem , Bloqueadores dos Canais de Cálcio/isolamento & purificação , Ciclofosfamida/administração & dosagem , Cistite/induzido quimicamente , Masculino , Camundongos , Neuropeptídeos/administração & dosagem , Neuropeptídeos/isolamento & purificação , Venenos de Aranha/administração & dosagem , Venenos de Aranha/isolamento & purificação , Medula Espinal/efeitos dos fármacosRESUMO
The rat posterodorsal medial amygdala (MePD) links emotionally charged sensory stimuli to social behavior, and is part of the supramedullary control of the cardiovascular system. We studied the effects of microinjections of neuroactive peptides markedly found in the MePD, namely oxytocin (OT, 10 ng and 25 pg; n=6/group), somatostatin (SST, 1 and 0.05 µM; n=8 and 5, respectively), and angiotensin II (Ang II, 50 pmol and 50 fmol; n=7/group), on basal cardiovascular activity and on baroreflex- and chemoreflex-mediated responses in awake adult male rats. Power spectral and symbolic analyses were applied to pulse interval and systolic arterial pressure series to identify centrally mediated sympathetic/parasympathetic components in the heart rate variability (HRV) and arterial pressure variability (APV). No microinjected substance affected basal parameters. On the other hand, compared with the control data (saline, 0.3 µL; n=7), OT (10 ng) decreased mean AP (MAP50) after baroreflex stimulation and increased both the mean AP response after chemoreflex activation and the high-frequency component of the HRV. OT (25 pg) increased overall HRV but did not affect any parameter of the symbolic analysis. SST (1 µM) decreased MAP50, and SST (0.05 µM) enhanced the sympathovagal cardiac index. Both doses of SST increased HRV and its low-frequency component. Ang II (50 pmol) increased HRV and reduced the two unlike variations pattern of the symbolic analysis (P<0.05 in all cases). These results demonstrate neuropeptidergic actions in the MePD for both the increase in the range of the cardiovascular reflex responses and the involvement of the central sympathetic and parasympathetic systems on HRV and APV.
Assuntos
Pressão Arterial/efeitos dos fármacos , Barorreflexo/efeitos dos fármacos , Complexo Nuclear Corticomedial/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Neuropeptídeos/farmacologia , Vigília , Análise de Variância , Angiotensina II/administração & dosagem , Animais , Encéfalo/anatomia & histologia , Sistema Cardiovascular/inervação , Complexo Nuclear Corticomedial/metabolismo , Hemodinâmica/efeitos dos fármacos , Masculino , Microinjeções , Neuropeptídeos/administração & dosagem , Ocitocina/administração & dosagem , Sistema Nervoso Parassimpático/efeitos dos fármacos , Ratos Wistar , Somatostatina/administração & dosagem , Estatísticas não Paramétricas , Sistema Nervoso Simpático/efeitos dos fármacos , Dispositivos de Acesso VascularRESUMO
The effects of intraperitoneal injections of cholecystokinin (CCK), apelin, ghrelin, and orexin on food intake were examined in the blind cavefish Astyanax fasciatus mexicanus. CCK (50ng/g) induced a decrease in food intake whereas apelin (100ng/g), orexin (100ng/g), and ghrelin (100ng/g) induced an increase in food intake as compared to saline-injected control fish. In order to better understand the central mechanism by which these hormones act, we examined the effects of injections on the brain mRNA expression of two metabolic enzymes, tyrosine hydroxylase (TH), and mechanistic target of rapamycin (mTOR), and of appetite-regulating peptides, CCK, orexin, apelin and cocaine and amphetamine regulated transcript (CART). CCK injections induced a decrease in brain apelin injections, apelin injections induced an increase in TH, mTOR, and orexin brain expressions, orexin treatment increased brain TH expression and ghrelin injections induced an increase in mTOR and orexin brain expressions. CART expression was not affected by any of the injection treatments. Our results suggest that the enzymes TH and mTOR and the hormones CCK, apelin, orexin, and ghrelin all regulate food intake in cavefish through a complex network of interactions.
Assuntos
Apetite/fisiologia , Encéfalo/efeitos dos fármacos , Colecistocinina/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Grelina/administração & dosagem , Hormônios/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Neuropeptídeos/administração & dosagem , Sirolimo/farmacologia , Tirosina 3-Mono-Oxigenase/metabolismo , Animais , Encéfalo/enzimologia , Characidae , Quimiocinas/administração & dosagem , Colagogos e Coleréticos/administração & dosagem , Imunossupressores/farmacologia , Neurotransmissores/administração & dosagem , Orexinas , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Tirosina 3-Mono-Oxigenase/antagonistas & inibidores , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
This paper describes an experimental approach based on nanotechnology for assessing the chronic actions of short-lived neuropeptides at specific sites of the brain. This methodology combines the advantages of two different techniques: the microinjection of a suspension of peptide-containing liposomes into a specific site of the brain, and the use of liposomes as a local and sustained release nanosystem of the peptide.
Assuntos
Lipossomos/química , Microinjeções/métodos , Neuropeptídeos/química , Neuropeptídeos/metabolismo , Animais , Encéfalo/metabolismo , Neuropeptídeos/administração & dosagem , RatosRESUMO
N-acetylaspartic acid (NAA) is the biochemical hallmark of Canavan Disease, an inherited metabolic disease caused by deficiency of aspartoacylase activity. NAA is an immediate precursor for the enzyme-mediated biosynthesis of N-acetylaspartylglutamic acid (NAAG), whose concentration is also increased in urine and cerebrospinal fluid of patients affected by CD. This neurodegenerative disorder is clinically characterized by severe mental retardation, hypotonia and macrocephaly, and generalized tonic and clonic type seizures. Considering that the mechanisms of brain damage in this disease remain not fully understood, in the present study we investigated whether intracerebroventricular administration of NAA or NAAG elicits oxidative stress in cerebral cortex of 30-day-old rats. NAA significantly reduced total radical-trapping antioxidant potential, catalase and glucose 6-phosphate dehydrogenase activities, whereas protein carbonyl content and superoxide dismutase activity were significantly enhanced. Lipid peroxidation indices and glutathione peroxidase activity were not affected by NAA. In contrast, NAAG did not alter any of the oxidative stress parameters tested. Our results indicate that intracerebroventricular administration of NAA impairs antioxidant defenses and induces oxidative damage to proteins, which could be involved in the neurotoxicity of NAA accumulation in CD patients.
Assuntos
Ácido Aspártico/análogos & derivados , Doença de Canavan/metabolismo , Córtex Cerebral/metabolismo , Neurotoxinas/toxicidade , Estresse Oxidativo/fisiologia , Animais , Antioxidantes/metabolismo , Ácido Aspártico/administração & dosagem , Ácido Aspártico/metabolismo , Ácido Aspártico/toxicidade , Dano Encefálico Crônico/etiologia , Dano Encefálico Crônico/metabolismo , Doença de Canavan/complicações , Catalase/efeitos dos fármacos , Catalase/metabolismo , Córtex Cerebral/efeitos dos fármacos , Dipeptídeos/administração & dosagem , Dipeptídeos/metabolismo , Dipeptídeos/toxicidade , Modelos Animais de Doenças , Glucosefosfato Desidrogenase/efeitos dos fármacos , Glucosefosfato Desidrogenase/metabolismo , Glutationa Peroxidase/efeitos dos fármacos , Glutationa Peroxidase/metabolismo , Injeções Intraventriculares , Peroxidação de Lipídeos , Masculino , Neuropeptídeos/administração & dosagem , Neuropeptídeos/metabolismo , Neuropeptídeos/toxicidade , Neurotoxinas/administração & dosagem , Neurotoxinas/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
In the present study, the acute behavioral and ingestive effects of ICV injections of mammalian orexin-A (ORXA; vehicle, 0.2, 0.6 or 2 nmol) and of orexin-B (ORXB; vehicle, 0.2, 0.6 or 2 nmol), as well as possible long-term effects (through 24 h of continuous intake monitoring after 0.6 nmol of ORXA or ORXB) of these treatments in food/water intake and in blood levels of metabolic fuels (free fatty acids and glucose, after 0.2 or 0.6 nmol of ORXA) were examined in adult male pigeons. Both ORXA and ORXB treatments failed to produce acute (1-3 h) or long-term effects on feeding and drinking behaviors, and did not change blood free fatty acids and glucose 15 and 30 min after treatments, as compared to vehicle-treated animals. However, ORXA (but not ORXB) treatments evoked a dose-related, intense increase in exploratory behaviors, associated to reduced time spent in alert immobility and sleep-typical postures. These data substantiate the lack of orexigenic effects of ORXs in avian species, and suggest that an important role in vigilance control may represent a conserved functional attribute of orexinergic circuits in vertebrates.
Assuntos
Comportamento Animal/efeitos dos fármacos , Comportamento de Ingestão de Líquido/efeitos dos fármacos , Comportamento Alimentar/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/farmacologia , Neuropeptídeos/farmacologia , Animais , Columbidae/metabolismo , Relação Dose-Resposta a Droga , Injeções Intraventriculares , Peptídeos e Proteínas de Sinalização Intracelular/administração & dosagem , Masculino , Neuropeptídeos/administração & dosagem , Orexinas , Sono/efeitos dos fármacosRESUMO
Cortistatin (CST) is a recently described neuropeptide with high structural homology with somatostatin. Its mRNA is restricted to gamma amino butyric acid (GABA)-containing cells in the cerebral cortex and hippocampus. CST modulates the electrophysiology of the hippocampus and cerebral cortex of rats; hence, it may be modulating mnemonic processes. In this study, we have evaluated the effect of CST and somatostatin (SS) on short- and long-term memory (STM and LTM, respectively), as well as on the extinction of the behavior by using the footshock passive avoidance behavioral test. In addition, we tested the ability of both neuropeptides to affect the generation of cAMP in hippocampal neurons in culture. Results showed that the administration of either CST or SS into the hippocampal CA1 deteriorates memory consolidation in a dose-response fashion and facilitates the extinction of the learned behavior. CST was more potent than SS. Likewise, CST increases cAMP while SS decreases it. These results strongly support a modulatory role for CST in memory processes.
Assuntos
Memória/fisiologia , Neuropeptídeos/metabolismo , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Células Cultivadas , AMP Cíclico/biossíntese , Relação Dose-Resposta a Droga , Extinção Psicológica/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Técnicas Imunoenzimáticas , Masculino , Memória/efeitos dos fármacos , Neurônios/citologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neuropeptídeos/administração & dosagem , Ratos , Ratos Wistar , Somatostatina/administração & dosagem , Somatostatina/metabolismoRESUMO
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
El amplio rango de actividades biologicas que tienen los NP llevan a pensar sobre su accion sobre ciertos sintomas del asma. Se han enfatizado la potencia espasmogenica, seguida de edema y participacion de los leucocitos. La capacidad de contraer el musculo liso sugiere un papel en la regulacion del tono de las vias aereas y conversion de la respuesta fisiologica en los sintomas del asma clinico. Su propiedad de inducir edema hace pensar en un posible rol en la presencia de hiper-reactividad bronquial.