Neuroscience
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The sensitization of peripheral nociceptors by different prostaglandins was studied in an in vitro preparation of the neonatal spinal cord with functionally attached tail. Nociceptors in the rat tail were activated by chemical (bradykinin, capsaicin) and thermal (heated saline) stimuli and responses were recorded as a depolarization of a ventral root in the lumbar region of the spinal cord (L3-L5). Responses evoked by bradykinin, capsaicin or submaximal thermal stimulation were enhanced in the presence of prostaglandin E1, prostaglandin E2, prostaglandin F2 alpha, prostaglandin I2 and the stable prostaglandin I2 analogue cicaprost, but not by prostaglandin D2. ⋯ Immunocytochemical localization of protein gene product 9.5 and growth associated protein 43 indicated that the neuronal innervation of subepidermal skin layers was preserved in the tail following removal of the most superficial skin layers which was performed in order to facilitate drug access to peripheral nerve endings. These results indicate that different prostaglandins and cyclic AMP sensitize peripheral nerve endings to noxious stimulation without directly activating nociceptors. The stimulation of nociceptors by bradykinin was only partially mediated via arachidonic acid metabolites whereas bradykinin-induced sensitization was independent of cyclo-oxygenase activity.
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We examined the effects of the 5-hydroxytryptamine2 receptor agonist, (+-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, on spontaneous and evoked discharge of locus coeruleus neurons in the rat. Extracellular recordings were obtained from single locus coeruleus neurons while (+-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane was injected systemically or locally into the locus coeruleus. Systemic, but not local, administration of (+-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane decreased spontaneous discharge of locus coeruleus neurons in a dose-dependent manner while simultaneously increasing responses evoked by somatosensory stimulation, consistent with previous studies using 5-hydroxytryptamine2 agonists. ⋯ Both of these effects could be completely reversed by systemic administration of the 5-hydroxytryptamine2 receptor antagonist, ketanserin. Furthermore, we report that: (i) the (+/-)1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane-induced decrease in spontaneous firing was blocked by local infusion of the GABA antagonists bicuculline or picrotoxin into the locus coeruleus, but not by local infusion of the alpha-2 adrenoceptor antagonist, idazoxan; and (ii) the enhancement of locus coeruleus sensory responses after high-intensity stimulation was blocked by local application of the selective antagonist of N-methyl-D-aspartate receptors, 2-amino-5-phosphonopentanoic acid, but not by local infusion of the preferential antagonist of non-N-methyl-D-aspartate receptors, 6-cyano-7-nitroquinoxaline-2,3-dione. Together, these results lead us to propose that systemic 5-hydroxytryptamine2 agonists influence locus coeruleus indirectly, causing tonic activation of a GABAergic input to the locus coeruleus, and facilitating sensory inputs that act via excitatory amino acid receptors within locus coeruleus.
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In this study we have described the ontogeny of immunoreactivity for calcitonin gene-related peptide, substance P and glutamate in primary sensory neurons, and for serotonin in the sacral spin cord, of fetal sheep (n = 37) from 56 to 140 days of gestation (term = 146 days). A few fine, varicose fibres immunoreactive for calcitonin gene-related peptide were present in Lissauer's tract, the dorsolateral funiculus and in laminae I and V in the dorsal horn of the spinal cord at 56-61 days of gestation. At this age, two groups of intensely staining immunoreactive cells were present in the motoneuron pool in laminae VIII and IX in the ventral horn of the spinal cord. ⋯ Immunoreactivity for glutamate and neuropeptides appeared in the cells and fibres of dorsal root ganglia at 97-100 days. In the skin, immunoreactivity for calcitonin gene-related peptide and substance P was present at 85 days, some time after its appearance in the cord. Fibres immunoreactive for serotonin appeared in lamina I, at the neck of the dorsal horn and in the ventral horn at 83 days of gestation.(ABSTRACT TRUNCATED AT 400 WORDS)
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The present study determined the effects of chronic intranigral injections of recombinant human brain-derived neurotrophic factor (1 micrograms) every second day for 19 days on the functional capacity of dopaminergic neurons of the nigrostriatal pathway of unlesioned adult rats. In animals chronically treated with brain-derived neurotrophic factor, we observed amphetamine (5 mg/kg)-induced circling behavior directed toward the neurotrophin-injected side (33 turns/5 min). The behavioral asymmetry was paralleled by reductions of striatal [3H]dopamine uptake (27%), tyrosine hydroxylase activity (68%), dopamine content (36%) and [3H]mazindol binding site density (35%) on the same side as brain-derived neurotrophic factor treatment. ⋯ Chronic intranigral brain-derived neurotrophic factor treatment did not attenuate nor did it exacerbate the medial forebrain bundle lesion-induced decreases of dopaminergic parameters in either the substantia nigra or striatum. The results of the present study indicate that chronic intranigral administration of brain-derived neurotrophic factor to normal adult rats induces a dopaminergic hypofunction in the striatum which is manifested behaviorally by amphetamine-induced rotations. The brain-derived neurotrophic factor-induced striatal function is not the result of significant cell loss at the levels of the substantia nigra, but seems to be related to brain-derived neurotrophic factor-induced down-regulation of dopaminergic-specific proteins.(ABSTRACT TRUNCATED AT 400 WORDS)
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Whole cell patch-clamp recordings were made from substantia gelatinosa neurons in the thick slice of the adult rat spinal cord, which retained an attached dorsal root to study the pharmacological properties of spontaneous and primary afferent fibre-evoked synaptic currents. The majority of substantia gelatinosa neurons tested exhibited miniature excitatory postsynaptic currents in the presence of tetrodotoxin (0.5 microM). Stimulation of primary afferent A delta fibres evoked monosynaptic and/or polysynaptic excitatory postsynaptic currents. ⋯ In Mg(2+)-free solution, however, 6-cyano-7-nitroquinoxaline-2,3-dione reduced but did not abolish the miniature excitatory postsynaptic currents, leaving the miniature excitatory postsynaptic currents with a small amplitude and a slow time course, which were abolished by 2-amino-5-phosphonovaleric acid. At holding potentials more positive than -60 mV, stimulation of A delta fibres evoked outward postsynaptic currents in 11 out of 28 substantia gelatinosa neurons. The evoked inhibitory postsynaptic currents were abolished in seven out of 11 neurons by either strychnine (0.5 microM) or bicuculline (10 microM), and in the remaining four neurons by the combination of both antagonists.(ABSTRACT TRUNCATED AT 250 WORDS)