Neuroscience
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The transmitter mechanism of a long-lasting descending inhibition of the monosynaptic reflex was investigated in the isolated spinal cord of the neonatal rat. The monosynaptic reflex elicited by dorsal root stimulation was recorded extracellularly from a lumbar ventral root (L3-L5). Electrical stimulation of the upper thoracic part of the hemisected cord caused an inhibition lasting about 40 s of the monosynaptic reflex. ⋯ Besides ketanserin, the descending inhibition was blocked by ritanserin, haloperidol, and pipamperone, which have affinities to 5-hydroxytryptamine2 receptors, and also by spiperone and methiothepin, which are antagonists at both 5-hydroxytryptamine1 and 5-hydroxytryptamine2 receptors (all 1 microM). On the other hand, a 5-hydroxytryptamine1C and 5-hydroxytryptamine2 antagonist, mesulergine (1 microM), and 5-hydroxytryptamine3 antagonists, ICS 205-930 and quipazine (both 1 microM), did not depress either the descending inhibition or the 5-hydroxytryptamine-evoked inhibition of the monosynaptic reflex. The results with these antagonists favor the involvement of 5-hydroxytryptamine2 receptors although the results with mesulergine disagree with this notion. 5-Hydroxytryptamine1 agonists, such as 8-hydroxy-2-(di-n-propylamino)tetralin, buspirone, and 5-carboxyamidotryptamine, and a 5-hydroxytryptamine3 agonist, 2-methyl-5-hydroxytryptamine, induced a long-lasting inhibition of the monosynaptic reflex, which was blocked by ketanserin whereas a 5-hydroxytryptamine2 agonist, S-(+)-alpha-methyl-5-hydroxytryptamine, evoked a biphasic inhibition, in which only the later component was blocked by ketanserin.(ABSTRACT TRUNCATED AT 400 WORDS)
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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.
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Recordings were made from neurons in subnucleus reticularis dorsalis of the rat. Two populations of neurons could be distinguished: those with total nociceptive convergence which were driven by activating A delta- and C-fibers from any part of the body and those with partial nociceptive convergence which were driven by activating A delta-fibers from any part of the body or C-fibers from some, mainly contralateral, regions. The effects on subnucleus reticularis dorsalis neurons of manual acupuncture, performed by a traditional Chinese acupuncturist at the "Renzhong", "Sousanli", "Changqiang", and "Zusanli" acupoints and at a non-acupoint next to "Zusanli", were studied. ⋯ No differences were found between the capacities to activate subnucleus reticularis dorsalis neurons of the "Zusanli" point and the adjacent non-acupoint, no matter whether these were stimulated ipsi- or contralaterally; this suggests a lack of topographical specificity in the activation of these neurons. Since subnucleus reticularis dorsalis neurons are activated exclusively or preferentially by noxious inputs, it is concluded that the signals elicited by manual acupuncture travel through pathways responsible for the transmission of nociceptive information. Since acupuncture, a manoeuvre which is known to elicit widespread extrasegmental antinociceptive effects, activates subnucleus reticularis dorsalis neurons which, anatomically, send dense projections to the dorsal horn at all levels of the spinal cord, we would suggest that this structure may be involved not only in signalling pain but also in modulating pain by means of spino-reticulo-spinal feed-back mechanisms.