Neuroscience
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Bilateral lesions of the ventrolateral caudal periaqueductal gray inhibit lordosis and kyphosis, the postures of female sexual receptivity and maternal nursing that are characterized respectively by dorsoflexion and ventroflexion of the spinal column. These lesions also inhibit the solicitation behaviors that accompany lordosis, but they do not impair retrieval or licking of pups. We tested the hypothesis that reproductive behaviors affected by these lesions are tonically inhibited by activity of the GABA(A) receptor via site-specific manipulations of receptor activity. ⋯ These findings suggest that the reproductive postures of female rats, lordosis and kyphosis, as well as sexual solicitations, are tonically inhibited by the neurotransmitter GABA within the ventrolateral caudal periaqueductal gray in the midbrain. In contrast, retrieval and licking of pups appear to be under separate neurochemical or neuroanatomical control, or both. Further, this tonic inhibition is likely relieved by excitatory somatosensory inputs to this site, from mounting and suckling respectively.
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Both myelinated and unmyelinated afferents are implicated in transmitting diabetic neuropathic pain. Although unmyelinated afferents are generally considered to play a significant role in diabetic neuropathic pain, pathological changes in diabetic neuropathy occur mostly in myelinated A-fibers. In the present study, we first examined the role of capsaicin-sensitive C-fibers in the development of allodynia induced by diabetic neuropathy. ⋯ Furthermore, these afferent fibers had a lower threshold for activation and augmented responses to mechanical stimuli. Thus, our study suggests that capsaicin-sensitive C-fiber afferents are not required in the development of allodynia in this rat model of diabetes. Our electrophysiological data provide substantial new evidence that the abnormal sensory input from Adelta- and Abeta-fiber afferents may play an important role in diabetic neuropathic pain.
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Effects of C-fiber activation on type I slowly adapting mechanoreceptor responses were investigated in a rat in vitro nerve-skin preparation using controlled mechanical stimuli. Two changes in behavior were evoked by antidromic C-fiber stimulation: (1). The type I response to mechanical stimuli was modulated in a graded fashion by antidromic C-fiber activation. ⋯ Immunohistochemical staining revealed both substance P- and calcitonin gene-related peptide-like immunoreactivity in small unmyelinated nerve fibers entering the touch dome. These results support the concepts that (1). the type I slowly adapting mechanoreceptor in rat receives input from nociceptive terminals within the touch dome. (2). The function of type I slowly adapting mechanoreceptors is modulated by axon reflex activation of nociceptor terminals, which may play a role in altering the type I response during states of mechanical allodynia and have paracrine and autocrine influences on maintenance of touch dome structure.
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Cortical malformations resulting from aberrant brain development can be associated with mental retardation, dyslexia, and intractable forms of epilepsy. Despite emerging interest in the pathology and etiology of cortical malformations, little is known about the phenotype of cells within these lesions. In utero exposure to the DNA methylating agent methylazoxymethanol acetate (MAM) during a critical stage in neurodevelopment results in animals with distinct clusters of displaced neurons in hippocampus, i.e. nodular heterotopia. ⋯ Normotopic CA1 pyramidal neurons (e.g. pyramidal cells with normal lamination adjacent to a heterotopia) in the MAM brain exhibited molecular and electrophysiological properties that were nearly identical to those of age-matched CA1 pyramidal neurons from control rats. We conclude that neuronal heterotopiae in the hippocampus of MAM-exposed rats are comprised of neurons with a Layer II-III supragranular cortex phenotype. The MAM model, therefore, may serve as a useful tool in examination of the factors influencing aberrant brain development and epilepsy.
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The mechanisms involved in morphine tolerance are poorly understood. It was reported by our group that calcitonin gene-related peptide (CGRP)-like immunoreactivity (IR) was increased in the spinal dorsal horn during morphine tolerance [Ménard et al. (1996) J. Neurosci. 16, 2342-2351]. ⋯ Moreover, a combined treatment with DAMGO and a PKC inhibitor (chelerythrine chloride or Gö 6976) was able to block the effects of the opioid on increased CGRP-like IR. These data suggest that the three opioid receptors may be involved in the induction of CGRP and SP observed following chronic exposure to opiates, and that PKC probably plays a role in the signaling pathway leading to the up-regulation of these neuropeptides. These findings further validate the DRG cell culture as a suitable model to study intracellular pathways that govern changes seen following repeated opioid treatments possibly leading to opioid tolerance.