Neuroscience
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The effect of capsaicin on voltage-activated calcium currents was investigated in voltage-clamped somata of cultured adult rat dorsal root ganglion neurons. About half the neurons studied were sensitive to capsaicin, which induced an inward current at negative membrane potentials accompanied by an increase in membrane conductance. In the sensitive neurons capsaicin inhibited voltage-activated calcium current to an extent that depended on the size and duration of the capsaicin-induced inward current. ⋯ Substituting Ca with Co did not prevent the prolonged block of calcium channels. It is concluded that the inhibition of voltage-activated calcium currents by capsaicin is secondary to increased intracellular Ca levels due to calcium entry through capsaicin-activated cation-specific ion channels in the plasma membrane. Long-lasting inhibition of voltage-activated calcium channels may contribute to the mechanism of the analgesic and anti-inflammatory effects of capsaicin through inhibition of neurotransmitter release from central and peripheral terminals of primary afferent nociceptive neurons.
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The efferent projections of the core and shell areas of the nucleus accumbens were studied with a combination of anterograde and retrograde tract-tracing methods, including Phaseolus vulgaris-leucoagglutinin, horseradish peroxidase and fluorescent tracers. Both the core and shell regions project to pallidal areas, i.e. ventral pallidum and entopeduncular nucleus, with a distinct topography in the sense that the core projection is located in the dorsolateral part of ventral pallidum, whereas the shell projects to the medial part of the subcommissural ventral pallidum. Both regions of the accumbens also project to mesencephalon with a bias for the core projection to innervate the substantia nigra-lateral mesencephalic tegmentum, and for the shell projection to reach primarily the ventral tegmental-paramedian tegmentum area. ⋯ The shell, however, has additional features that are reminiscent of the recently described extended amygdala [Alheid G. F. and Heimer L. (1988) Neuroscience 27, 1-39; de Olmos J. S. et al. (1985) In The Rat Nervous System, pp. 223-334]; in fact, the possibility exists that the shell represents a transitional zone that seems to characterize most of the fringes of the striatal complex, where it adjoins the extended amygdala.
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In anaesthetized rats, recordings were made from nociceptive dorsal horn neurons with convergent input from the skin and deep somatic tissues. The results of a previous study have shown that in these neurons the input from deep nociceptors is subjected to a much stronger tonic descending inhibition than is the input from cutaneous nociceptors. The aim of the present study was to find out whether at supraspinal levels opioidergic, adrenergic, or serotoninergic transmitters are involved in this quite specific inhibition of deep nociception. ⋯ In contrast, supraspinal adrenergic and serotoninergic mechanisms do not appear to contribute to the tonic inhibition. The data confirm and extend previous results which suggested that a particular portion of the descending antinociceptive system may act mainly on the input from deep nociceptors. Pharmacologically, this particular portion seems to be opioidergic in nature.
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In an earlier report, we demonstrated that subcutaneous injection of formalin in the rat hindpaw evokes a characteristic pattern of expression of the fos protein product of the c-fos protooncogene in spinal cord neurons, and that systemic morphine reversed the fos-like immunoreactivity in a dose-dependent, naloxone-reversible manner. The present study compared the effects of intracerebroventricular administration of the mu-selective opioid ligand [D-Ala2, NMe-Phe4, Gly-ol5] enkephalin, on the pain behavior and spinal cord fos-like immunoreactivity produced by subcutaneous formalin. Formalin injection produced a biphasic pain behavioral response which lasted about 1 h. ⋯ Since the potencies for inhibition of pain behavior and fos-like immunoreactivity in the neck and ventral horn were comparable, these data suggest that the activity of neurons in these regions is directly related to the pain behavior produced by nociceptive inputs. Finally, we found that bilateral, midthoracic lesions of the dorsal part of the lateral funiculus blocked both the antinociception and fos suppression produced by intracerebroventricular [D-Ala2, NMe-Phe4, Gly-ol5]enkephalin. These results are consistent with the hypothesis that the analgesic action of supraspinally administered opiates results from an increase in descending inhibitory controls that regulate the firing of subpopulations of spinal cord nociresponsive neurons.
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A novel mechanism for regulating dopamine activity in subcortical sites and its possible relevance to schizophrenia is proposed. This hypothesis is based on the regulation of dopamine release into subcortical regions occurring via two independent mechanisms: (1) transient or phasic dopamine release caused by dopamine neuron firing, and (2) sustained, "background" tonic dopamine release regulated by prefrontal cortical afferents. Behaviorally relevant stimuli are proposed to cause short-term activation of dopamine cell firing to trigger the phasic component of dopamine release. ⋯ In this way, tonic dopamine release would set the background level of dopamine receptor stimulation (both autoreceptor and postsynaptic) and, through homeostatic mechanisms, the responsivity of the system to dopamine in these sites. In schizophrenics, a prolonged decrease in prefrontal cortical activity is proposed to reduce tonic dopamine release. Over time, this would elicit homeostatic compensations that would increase overall dopamine responsivity and thereby cause subsequent phasic dopamine release to elicit abnormally large responses.