Neuroscience
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We have analysed some behavioral, neuroendocrine and serotonergic consequences of a single (30-min) social defeat followed by 14-18 h of sensory contact with the aggressor, in Lewis rats, an inbred strain highly sensitive to chronic social stressors [Berton O. et al. (1998) Neuroscience 82, 147-159]. In addition, we have investigated how the aforementioned consequences are affected by pretreatment with the selective serotonin reuptake inhibitor, fluoxetine (7.5 mg/kg/day for 21 days). A single social defeat triggered hypophagia and body weight loss, and increased anxiety in the elevated plus-maze. ⋯ Except for a decrease in midbrain serotonin transporter density, fluoxetine did not affect the other serotonergic indices analysed herein, i.e. serotonin-1A and serotonin-2A receptor densities, serotonin synthesis/metabolism. A single social defeat in Lewis rats produces behavioral and endocrine alterations that may model some aspects of human anxiety disorders. In this paradigm, prior fluoxetine treatment is endowed with adaptive behavioral, and possibly neuroendocrine, effects without affecting the key elements of central serotonergic systems analysed herein.
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The classic opioid peptide, enkephalin, and the novel member of the opioid family, nociceptin/orphanin FQ, inhibit the spontaneous electrical activity of neurons recorded from the rostral ventrolateral medulla, presumably cardiovascular neurons. In this study, the putative effects of endomorphin-1 and endomorphin-2, the newly discovered endogenous ligands for the micro-opioid receptor, on the electrical activity of rostral ventrolateral medulla neurons were investigated in rat brain slices in vitro. Like enkephalin and nociceptin, perfusion of endomorphin-1 or endomorphin-2 profoundly inhibited spontaneous discharges of 43% and 38% of the medullary neurons, respectively. ⋯ The selective mu antagonist, beta-funaltrexamine, prevented the neuronal inhibition induced by endomorphins, but not by enkephalin and nociceptin. Neither naloxone nor beta-funaltrexamine alone had a significant effect on the firing rate of the neurons. These results demonstrate that endomorphin-1 and, to a lesser extent, endomorphin-2 exert an inhibitory modulation of the electrical activity of rostral ventrolateral medulla neurons, which is mediated through the stimulation of mu-opioid receptors.
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We previously presented evidence [Nagy et al. (1997) Neuroscience 78, 533-548] that, in addition to their ubiquitous expression of connexin43, astrocytes produce a second connexin suggested to be connexin30, a recently discovered member of the family of gap junction proteins. A connexin30 specific antibody was subsequently developed and utilized here to confirm and extend our earlier observations. On western blots, this antibody detected a 30,000 mol. wt protein in rat, mouse, cat and human brain, and exhibited no cross-reaction with connexin43, connexin26 or any other known connexins expressed in brain. ⋯ In contrast to regional connexin43 expression, diencephalic and hindbrain areas exhibited considerably greater expression than forebrain areas, subcortical perivascular astrocytic endfeet were more heavily labelled for connexin30, white matter tracts such as corpus callosum, internal capsule and anterior commissure were devoid of connexin30, and appreciable levels of connexin30 during development were not seen until about postnatal day 15. These results indicate that connexin30 is expressed by gray, but not white matter astrocytes, its distribution is highly heterogeneous in gray matter, it is co-localized with connexin43 at astrocytic gap junctions where it forms homotypic or heterotypic junctions, and its emergence is delayed until relatively late during brain maturation. Taken together, these results suggest that astrocytic connexin30 expression at both regional and cellular levels is subject to regulation in adult brain as well as during brain development.
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The immunocytochemical distribution of retinoid receptors has been analysed in the mouse adult central nervous system. All retinoic acid receptors (alpha, beta and gamma) and retinoid X receptors (alpha, beta and gamma) were detected and found to exhibit specific patterns of expression in various areas of the telencephalon, diencephalon and rhombencephalon. The protein localization of several retinoic acid receptors and retinoid X receptors did not correlate with the distribution of the corresponding RNA transcripts, as studied by in situ hybridization and RNase protection assays. This suggests that the expression of retinoid receptors could be post-transcriptionally regulated, which may contribute to their specific localization in the adult nervous system.
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Extracellular levels of dopamine are increased in response to systemic administration of cocaine in several brain areas including the nucleus accumbens and medial prefrontal cortex. While the cocaine-induced increase in extracellular dopamine levels in the nucleus accumbens is augmented after repeated daily cocaine, the response of extracellular dopamine levels in the medial prefrontal cortex is attenuated. Since dopamine in the medial prefrontal cortex has an inhibitory effect on nucleus accumbens dopamine levels and locomotor activity, the role of medial prefrontal cortex dopamine tolerance in the expression of sensitized locomotor behavior was further examined by injection of D-amphetamine sulfate into the prelimbic portion of the medial prefrontal cortex just prior to cocaine challenge in cocaine-sensitized rats. ⋯ The results suggest that in rats sensitized to cocaine, decreased medial prefrontal cortex dopamine levels in response to cocaine challenge may contribute to behavioral sensitization. Furthermore, the data indicate the possibility that there is an optimal range at which medial prefrontal cortex amphetamine exerts maximal behavioral inhibition. These findings implicate a role for decreased cortical control in producing sensitized behavioral responding to cocaine.