Neuroscience
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In human neocortical slices obtained during epilepsy surgery, sharp waves have been described to appear spontaneously, the shape of which met all criteria of epileptiform field potentials. In the present investigation, the current sinks and sources underlying these potentials were analysed. The cortical tissue used in the present study was a small portion of the tissue blocks excised for treatment of pharmacoresistant focal epilepsy. ⋯ The results suggest that the supragranular layers, especially layer II, change qualitatively in functional organization in slices showing spontaneous discharges. We think that this special feature represents the function of the upper layers and can be blocked by bicuculline. This interpretation is supported by the observation that ictal discharges normally started in the upper layers in spontaneous and non-spontaneous slices, except for spontaneous slices with bicuculline, where the zone initiating discharges was translocated to deeper layers.
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We propose that the primary afferent depolarization that follows GABA(A) receptor activation in the spinal cord also occurs in the periphery. As evidence, the present study localizes beta2/beta3 and alpha1 subunits of the GABA(A) receptor on 10-14% of the unmyelinated primary afferents axons in the glabrous skin of the cat paw. Behavioral studies demonstrate that local peripheral injection of the GABA(A) agonist muscimol at a low concentration (2.0 microM) attenuates, and at a high concentration (1 mM) enhances, formalin-induced nociceptive behaviors. ⋯ Higher concentrations of muscimol further depolarize GABA(A) receptor-containing terminals, which then initiates action potentials in nociceptors analogous to the appearance of dorsal root reflexes that arise following activation of GABA(A) receptors on central primary afferent terminals. These latter events reverse the analgesic effects of GABA(A) ligands and lead to potentiation of nociceptive input. Thus, the present study provides anatomical and behavioral evidence supporting a bimodal role for GABA(A) receptors in the modulation of peripheral nociceptive transmission.
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The present study was carried out to evaluate the effect of morphine, cocaine and ethanol on the density of opioid receptors in the nucleus accumbens and striatum of rat brain. The animals were injected i.p. with morphine in a single dose 20 mg/kg, or twice daily for 10 days in increasing doses of 20-100 mg/kg. Cocaine was administered in a dose of 60 mg/kg/day following the "binge" paradigm, every hour for 3 h, one day (single treatment) or five days (chronic treatment). ⋯ A long-term intake of ethanol solution down-regulates mu opioid receptors in both structures, but has no effect on any type of delta receptors. Thus changes in the particular opioid receptor depend on the type of drug used. Furthermore, the most profound changes are observed after late withdrawal, which may play some role in maintaining the state of dependence.
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The interstitial nucleus of the posterior limb of the anterior commissure is, like the striatum, very rich in tyrosine hydroxylase and acetylcholinesterase, but on the basis of most other neurochemical criteria displays features that are typical of the extended amygdala (Alheid, de Olmos and Beltramino, 1995). Its afferent connections were examined in the rat with retrograde (cholera toxin B subunit) and anterograde (Phaseolus vulgaris leucoagglutinin) tracers and compared to those of the neighboring amygdalostriatal transition area and central amygdaloid nucleus. Deposits of cholera toxin B subunit in the interstitial nucleus of the posterior limb of the anterior commissure result in retrograde labeling that is similar to that seen after cholera toxin B subunit injections in the central amygdaloid nucleus. ⋯ The afferent connections of the zone traditionally termed amygdalostriatal transition area are in general similar to those of the caudate-putamen, which does not receive projections from the central extended amygdala. After cholera toxin B subunit injections in the caudoventral globus pallidus, a dense retrograde labeling is observed in the amygdalostriatal transition area and overlying striatum, but not in the interstitial nucleus of the posterior limb of the anterior commissure. Our results suggest that the interstitial nucleus of the posterior limb of the anterior commissure and the amygdalostriatal transition area are engaged in distinct forebrain circuits; the former is a dopamine-rich territory intimately related to the central ext
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It has been suggested that there are sex differences in the neural response to drugs of abuse. Previous studies have shown that, upon administration of morphine, the immediate early gene c-Fos is induced in the striatum, nucleus accumbens and cortex of the rat brain. This induction of c-Fos is reduced by administration of the N-methyl-D-aspartate receptor antagonist dizocilpine maleate. ⋯ In the caudate-putamen, morphine-induced c-Fos expression was significantly reduced by NPC-17742 (30 min before morphine) in males and completely blocked in females. These results suggest that the responses to both morphine and N-methyl-D-aspartate receptor antagonists differ between the sexes and emphasize that glutamate is involved in morphine-induced immediate early gene expression in the brain. These studies thus have important implications for gender differences in drug addiction.