Neuroscience
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The present investigation details the modulation of medullary dorsal horn neuron responses to excitatory amino acids and peripheral cutaneous stimuli by orphanin FQ (nociceptin), an endogenous ligand for the opioid receptor-like, receptor. Effects of orphanin FQ, administered microiontophoretically or given intracerebroventricularly, were tested on the responses of nociceptive-specific, wide dynamic range and low threshold neurons recorded in the superficial and deeper dorsal horn of the medulla (trigeminal nucleus caudalis) in anesthetized (urethane or pentobarbital) male rats. Microiontophoretic application of orphanin FQ reduced the N-methyl-D-aspartate-evoked responses in 86% (71/82) of neurons, and the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-evoked responses in 86% (30/35) of neurons. ⋯ Orphanin FQ reduced the N-methyl-D-aspartate-evoked responses in 85% (11/13) of neurons whereas the (+/-)-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid-evoked responses were facilitated in 69% (9/13) of neurons. We suggest that orphanin FQ produces a predominantly inhibitory effect on, (i) noxious stimuli evoked responses, (ii) excitatory amino acid receptor-mediated transmission and, (iii) the substance P-induced facilitation of the N-methyl-D-aspartate-evoked responses. We conclude that orphanin FQ primarily produced an antinociceptive action at the level of the dorsal horn of the medulla.
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Synaptic plasticity has been implicated in the mechanisms contributing to the shaping of the cortical circuits responsible for the transmission of the visual input in the rat primary visual cortex. However, the degree of plasticity of the thalamocortical synapse may change during development, perhaps reflecting the degree of stabilization of the circuitry subserving it. We have chosen the ability of this synapse to be first depressed and then potentiated as a specific indicator of its plasticity. ⋯ The decrease in this form of cortical synaptic plasticity closely matches the stabilization of the cortical circuitry towards an adult pattern of connectivity and function. Depressed cortical synapses cannot be potentiated in normal rats at postnatal 23, but they can be potentiated in rats reared in the dark from postnatal days 17 to 29. Moreover, application of brain-derived neurotrophic factor, known to be expressed in an activity-dependent manner, was able to restore the ability of synapses to be potentiated after long-term depression, thus indicating its important modulatory role in brain development.
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Nociceptive-specific and multireceptive neurons in the lumbar dorsal horn are excited by noxious stimuli applied to the hindpaw and inhibited by noxious stimuli applied to distant body regions. Given that at least a subset of these neurons are part of the circuit for nociceptive reflexes, inhibition of nociceptive-specific and multireceptive neurons should inhibit nociceptive reflexes. Unfortunately, previous attempts to test this hypothesis have been inconclusive because of methodological differences between electrophysiological and behavioral experiments. ⋯ However, inhibition of nociceptive-specific and multireceptive neurons concomitant with a shift in the hindlimb reflex from flexion to extension suggests that these neurons are part of the circuit for flexor reflexes specifically. Presumably, lateral inhibition from the flexor to extensor circuit allows for the release of hindlimb extension when neurons in the flexion circuit are inhibited by a distant noxious stimulus. Such a system reduces the chance of injury by allowing for withdrawal reflexes to a single noxious stimulus and escape reactions, such as running and jumping, to multiple noxious stimuli.
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The serotonin1A receptor partial agonist, buspirone, also displays antagonist properties at D2 receptors and is metabolized to the alpha2-adrenergic receptor antagonist, 1-(2-pyrimidinyl-piperazine). Herein, we examined mechanisms underlying the influence of buspirone alone, and in association with the serotonin reuptake inhibitor, fluoxetine, upon extracellular levels of serotonin, dopamine and noradrenaline simultaneously quantified in the frontal cortex of freely moving rats. Buspirone (0.01-2.5 mg/kg, s.c.) dose-dependently decreased dialysate levels of serotonin (-50%), and increased those of dopamine (+100%) and noradrenaline (+140%). ⋯ The facilitatory influence of buspirone upon resting and fluoxetine-stimulated dopamine and noradrenaline levels may also involve its serotonin1A properties. However, its principal mechanism of action in this respect is probably the alpha2-adrenergic antagonist properties of its metabolite, 1-(2-pyrimidinyl-piperazine). The present observations are of significance to experimental and clinical studies of the influence of buspirone upon depressive states, alone and in association with antidepressant agents.
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We have previously reported that an apparently uncomplicated Caesarean section birth produces long-term alterations in steady-state levels of dopamine in the central nervous system of the rat. In addition, adult rats that had been born by Caesarean section, either with or without acute global anoxia, showed markedly greater dopamine release from the nucleus accumbens in response to repeated stress, in comparison to vaginally born controls. The aim of the present study was to test whether these birth complications also result in long-term changes in behavior mediated by dopamine systems. ⋯ Animals delivered by Caesarean section + 15 min anoxia showed a significant increase in the duration and frequency of rearing, in comparison to controls. The pattern of behavioral changes observed indicates that, as adults, animals born by Caesarean section and by Caesarean section with added global anoxia both show heightened behavioral responses to amphetamine, in comparison to vaginally born animals. These findings highlight the sensitivity of dopamine pathways to variations in birth procedure and add experimental support to epidemiological evidence implicating birth complications in the pathophysiology of disorders involving central dopaminergic neurons, such as schizophrenia.