RESUMO
The effects of chronic mild prenatal stress on leukocyte infiltration into the airways was investigated in rat offspring. The chronic prenatal stress consisted of transitory and variable changes in the rat's living conditions. Offspring at adult age were actively sensitized (day 0) and intratracheally challenged (day 14) with ovalbumin. Bronchoalveolar lavage was performed in the offspring at 48 h after intratracheal challenge with ovalbumin. A significant increase in total leukocyte infiltration was observed in the non-stressed offspring group and this was associated with a marked recruitment of eosinophils without a significant effect on the influx of neutrophils and mononuclear cells. In the prenatal stressed offspring, the counts of both total leukocyte and eosinophils, as well as mononuclear cells, was increased by 50% compared to the non-stressed offspring. We provide here the first experimental evidence that chronic mild unpredictable prenatal stress produces a marked increase in the allergen-induced airway inflammation in the rat offspring.
Assuntos
Alérgenos , Hiper-Reatividade Brônquica/fisiopatologia , Inflamação/fisiopatologia , Complicações na Gravidez/psicologia , Efeitos Tardios da Exposição Pré-Natal , Estresse Psicológico , Animais , Hiper-Reatividade Brônquica/etiologia , Eosinófilos/fisiologia , Feminino , Privação de Alimentos , Abrigo para Animais , Contagem de Leucócitos , Ovalbumina , Gravidez , Ratos , Ratos Wistar , Privação de ÁguaRESUMO
We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP) and of some N- or C-terminal SP fragments (SPN and SPC, respectively) on retention test performance of avoidance learning. Male Wistar rats (220 to 280 g) were trained in an inhibitory step-down avoidance task and tested 24 h or 21 days later. Immediately after the training trial rats received an intraperitoneal injection of SP (50 micrograms/kg), SPN 1-7 (167 micrograms/kg) or SPC 7-11 (134 micrograms/kg). Control groups were injected with vehicle or SP 5 h after the training trial. The immediate post-training administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats tested 24 h or 21 days later, i.e., the retention test latencies of the SP and SPN groups were significantly longer (P < 0.05, Mann-Whitney U-test) during both training-test intervals. These observations suggest that the memory-enhancing effect of SP is long-lasting and that the amino acid sequence responsible for this effect is encoded by its N-terminal part.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Substância P/farmacologia , Animais , Masculino , Memória/fisiologia , Ratos , Ratos WistarRESUMO
This report summarizes a recent series of experiments dealing with the effect of peripheral (i.p.) administration of SP on the learning of avoidance and habituation tasks. In summary, the results from these studies show that peripheral post-training SP administration in rats enhances memory in a dose- and time-dependent way. The effect of substance P on retention was observed across tasks with different response requirements and in the absence of explicit punishment. The memory-enhancing effects are long-lasting, until 21 days post-training, and are mediated, at least in part, via interactions with the endogenous opioid system. The mnemotropic effects of peripherally administered SP are sensitive to the functional integrity of the vagus, suggesting that the vagus nerve may be one pathway by which systemic SP influences memory storage processes in the brain. Furthermore, the data indicated that these effects seemed to be encoded by different SP sequences, the N-terminal SP1-7, but not the C-terminal hepta- and hexapeptide sequences being responsible for the memory-promoting effects. Taken together, these studies strongly suggest that SP may be considered to have memory-promoting effects.
Assuntos
Memória/efeitos dos fármacos , Substância P/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Relação Dose-Resposta a Droga , Eletrochoque , Generalização da Resposta/efeitos dos fármacos , Injeções Intraperitoneais , Ratos , Estimulação Química , Substância P/administração & dosagem , Fatores de Tempo , VagotomiaRESUMO
We investigated the long-lasting effect of peripheral injection of the neuropeptide substance P (SP) and of some N- or C-terminal SP fragments (SPN and SPC, respectively) on retention test performance of avoidance learning. Male Wistar rats (220 to 280 g) were trained in an inhibitory step-down avoidance task and tested 24 h or 21 days later. Immediately after the training trial rats received an intraperitoneal injection of SP (50 mug/kg), SPN 1-7 (l67 mug/kg) or SPC 7-11 (l34 mug/kg). Control groups were injected with vehicle or SP 5 h after the training trial. The immediate post-training administration of SP and SPN, but not SPC, facilitated avoidance behavior in rats tested 24 h or 21 days later, i.e., the retention test latencies of the SP and SPN groups were significantly longer (P<0.05, Mann-Whitney U-test) during both training-test intervals. These observations suggest that the memory-enhancing effect of SP is long-lasting and that the amino acid sequence responsible for this effect is encoded by its N-terminal part.
Assuntos
Ratos , Animais , Masculino , Aprendizagem da Esquiva/efeitos dos fármacos , Memória/efeitos dos fármacos , Substância P/farmacologia , Memória/fisiologia , Ratos WistarRESUMO
The present study determined whether the effects of peripherally administered substance P on memory are mediated via activation of the vagus nerve. Rats were submitted to subdiaphragmatic vagotomy, sham vagotomy or non-operated, and trained in a step-down inhibitory avoidance task and tested 24 h later. Posttraining administration of 50 micrograms/kg of SP facilitated retention performance in non-operated and sham-operated groups. The facilitating effects of 50 micrograms/kg of SP was blocked by vagotomy, although vagotomy did not attenuate the memory-enhancing effects of larger doses (250 and 500 micrograms/kg). These results suggest that the mnemotropic effects of peripherally administered SP are sensitive to the functional integrity of the vagus nerve. Alternatively, the vagus nerve may be one pathway but not the only pathway by which systemic SP influences the memory storage processes in the brain.
Assuntos
Aprendizagem da Esquiva/fisiologia , Rememoração Mental/fisiologia , Inibição Neural/fisiologia , Substância P/fisiologia , Nervo Vago/fisiologia , Animais , Encéfalo/fisiologia , Eletrochoque , Medo/fisiologia , Feminino , Masculino , Ratos , Ratos Wistar , Tempo de Reação/fisiologia , Retenção Psicológica/fisiologiaRESUMO
The present study investigated the effects of post-trial systemic injections of the neurokinin substance P (SP) on inhibitory avoidance learning in rats treated with naloxone before conditioning and/or test trials. Rats were trained in a step-down or uphill inhibitory avoidance task and tested 24 h later. The animals received, 30 min before training and/or testing an i.p. injection of saline or naloxone (Nx) at doses of 0.5; 1.0; 5.0 or 50 mg/kg. Immediately after training they were administered SP 50 micrograms/kg or vehicle. Animals that received Nx both before conditioning and test trials (5.0 and 50 mg/kg), in combination with SP, showed better test performance for the uphill and step-down avoidance then those treated only with SP. Nx administered only before training (5.0 and 50 mg/kg) or before test (0.5 to 50 mg/kg) reduced the effects of SP. These data are discussed in terms of the possibility that Nx produces a state-dependent learning when combined with SP.
Assuntos
Memória/efeitos dos fármacos , Naloxona/farmacologia , Substância P/farmacologia , Animais , Aprendizagem da Esquiva/efeitos dos fármacos , Masculino , Ratos , Ratos Wistar , Vasodilatação/efeitos dos fármacosRESUMO
Experiments were carried out to investigate the effects of peripheral post-training administration of substance P (SP) and naloxone on learning. Rats were trained in three different avoidance tasks (uphill, step-down and alcove) and tested 24 h later. Thirty minutes before each trial (training and testing) rats received naloxone (0.5, 1, 5, or 50 mg/kg, ip) or saline. SP (50 micrograms/kg) or vehicle was administered ip immediately after training. Animals that received SP and SP in combination with naloxone (5 and 50 mg/kg) showed significantly better retention test performance for the uphill and step-down avoidance (P less than 0.05 when compared to control rats treated with vehicle). In the alcove task no influence of SP and/or naloxone was demonstrable, probably due to a ceiling effect. These results suggest that the memory enhancement effects observed are mediated, at least in part, via interactions between substance P and the endogenous opioid systems.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Naloxona/farmacologia , Retenção Psicológica/efeitos dos fármacos , Substância P/farmacologia , Animais , Masculino , Ratos , Ratos EndogâmicosRESUMO
This paper summarizes results of a series of experiments dealing with the effects of the neuropeptide substance P (SP) on avoidance learning and habituation. Several doses of SP (0.5, 5, 50, 100, 250, 500 micrograms/kg) were administered posttrial intraperitoneally (IP). Three inhibitory one-trial avoidance tasks were used; uphill, step-down and step-through (alcove). Habituation was measured in an open field by recording the number of rearings. The posttrial injection of SP facilitated avoidance responses as well as reduced rearing in a dose- and time-dependent way. Pretraining and pretest injections (IP) of naloxone facilitated avoidance behavior and potentiated the action of SP, also in a dose-dependent manner. These results demonstrate that: a) peripheral posttraining administration of SP enhances memory; b) SP facilitates not only aversive or positively motivated learning tasks, but also habituation, which is a form of learning that involves neither positive nor negative reinforces; c) SP does not exert its effect by a long-lasting proactive action on performance during the testing trial; d) naloxone potentiates the SP posttraining effect. These data, therefore, suggest that memory-enhancing effects of SP are, at least in part, mediated via interactions between this peptide and endogenous opioid systems.
Assuntos
Aprendizagem da Esquiva/efeitos dos fármacos , Habituação Psicofisiológica/efeitos dos fármacos , Aprendizagem/efeitos dos fármacos , Memória/efeitos dos fármacos , Naloxona/farmacologia , Substância P/farmacologia , AnimaisRESUMO
Experiments were carried out to investigate the effects of peripheral post-training administration of substance P (SP) and naloxone on learning. Rats were trained in three different avoidance tasks (uphill, step-down and alcove) and tested 24 h later. Thirty minutes before each trial (training and testing) rats received naloxone (0.5, 1, 5, or 50 mg/kg, ip) or saline. SP (50 microng/kg) or vehicle was administered ip immediately after training. Animals that received SP and SP in combination with naloxone (5 and 50 mg/kg) showed significantly better retention test performance for the uphill and step-down avoidance (P < 0.05 when compared to control rats treated with vehicle). In the alcove task no influence of SP and/or naloxone was demonstrable, probably due to a ceiling effect. These results suggest that the memory enhancement effects observed are mediated, at least in part, via interactions between substance P and the endogenous opioid systems