Brain research
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The constitutively expressed (CC) Homer protein Homer2a/b actively regulates behavioral and neurochemical sensitivity to cocaine in both rats and mice. The present study employed standard immunoblotting techniques to compare the effects of withdrawal from repeated cocaine (7 x 30 mg/kg) upon the protein expression of Homer2a/b with a related CC-Homer protein Homer1b/c, as well as their associated glutamate receptors, within brain regions implicated in cocaine addiction. To determine whether or not the observed cocaine-induced changes in Homer and glutamate receptor expression generalized across mammalian species, immunoblotting was conducted on tissue derived from both male Sprague-Dawley rats and male C57BL/6J mice. ⋯ Cocaine-induced increases in Homer1b/c, Homer2a/b, mGluR1a and NR2a were observed in the hippocampus of both rats and mice, while in dorsal striatum, NR2a levels were elevated but Homer and Group1 mGluR levels were unchanged. Thus, withdrawal from repeated cocaine alters the expression of CC-Homer isoforms and their associated glutamate receptors in a regionally-distinct manner. As CC-Homer proteins, Group1 mGluRs and NMDA receptors actively regulate cocaine-induced neuroplasticity in vivo, these data support the hypothesis that cocaine-induced changes in mGluR-Homer-NMDA signaling pathways may be important neuroadaptations mediating the enduring changes in behavior produced by repeated cocaine experience.
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Etifoxine (6-chloro-2-ethylamino-4-methyl-4-phenyl-4H-3,1-benzoxazine hydrochloride), a nonbenzodiazepine anxiolytic drug, potentiates GABA(A) receptor function perhaps through stimulation of neurosteroid biosynthesis. However, the exact mechanism of etifoxine action is not fully understood. In this study, we have assessed the possible role of GABAergic neurosteroid like allopregnanolone (ALLO) in the anxiolytic-like effect of etifoxine in rats using elevated plus maze test. ⋯ On the other hand, GABA(A) receptor antagonist, bicuculline or neurosteroid biosynthesis inhibitors like finasteride, indomethacin, trilostane or PBR antagonist, PK11195 significantly blocked the effect of etifoxine. Bilateral adrenalectomy did not influence anti-anxiety effect of etifoxine thereby ruling out contribution of adrenal steroids. Thus, our results provide behavioral evidence for the role of neurosteroids like ALLO in the anti-anxiety effect of etifoxine.
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Clinically, the overlap of gastroduodenal symptoms, such as visceral pain or hypersensitivity, is often observed in functional gastrointestinal disorders. The underlying mechanism may be related to intraspinal neuronal processing of noxious convergent inputs from the stomach and the intestine. The purpose of this study was to examine whether single low thoracic (T9-T10) spinal neurons responded to both gastric and duodenal mechanical stimulation. ⋯ In addition, 34/40 (85%) gastroduodenal convergent neurons had somatic receptive fields on the back, flank, and medial/lateral abdominal areas. These results suggested that superficial and deeper T9-T10 spinal neurons received innocuous and/or noxious convergent inputs from mechanical stimulation of the stomach and duodenum. Gastroduodenal convergent spinal neurons might contribute to intraspinal sensory transmission for cross-organ afferent-afferent communication between the stomach and duodenum and play a role in visceral nociception and reflexes.
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The hypothalamic-pituitary-adrenal (HPA) axis habituates, or gradually decreases its activity, with repeated exposure to the same stressor. During habituation, the HPA axis likely requires input from cortical and limbic regions involved in the processing of cognitive information that is important in coping to stress. Brain regions such as the medial prefrontal cortex (mPFC) are recognized as important in mediating these processes. ⋯ In the present experiments, we found that blockade of CRH receptors in the mPFC with the non-selective receptor antagonist d-Phe-CRH (50 ng or 100 ng) significantly inhibited HPA responses compared to vehicle regardless of whether animals were exposed to a single, acute 30 min restraint or to the eighth 30 min restraint. We also found that intra-mPFC injections of CRH (20 ng) significantly increased anxiety-related behavior in the elevated plus maze in both acutely and repeatedly restrained groups compared to vehicle. Together, these results suggest an excitatory influence of CRH in the mPFC on stress-induced HPA activity and anxiety-related behavior regardless of prior stress experience.
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Comparative Study
Nonprincipal neurons and CA2 pyramidal cells, but not mossy cells are immunoreactive for calcitonin gene-related peptide in the mouse hippocampus.
The distribution and morphological features of calcitonin gene-related peptide (CGRP) positive neurons in the mouse hippocampus were immunohistochemically analyzed, focusing on their differences between mice and rats. In contrast with those in the rat dentate gyrus, the mossy cell somata and their axon terminals in the mouse dentate gyrus were CGRP negative even after intraventricular colchicine injection. In the rat CA1-CA2-CA3 regions, there were two types of CGRP positive neurons, some of the CA3 pyramidal cells and relatively few nonprincipal neurons. ⋯ The CGRP positive nonprincipal neurons were apparently heterogeneous and further characterized immunohistochemically. Although there were significant regional differences in the chemical properties of the CGRP positive nonprincipal neurons, in the whole hippocampus, over 40% of CGRP positive nonprincipal neurons were also positive for parvalbumin, about 15% were positive for somatostatin and about 20% were positive for cholecystokinin, respectively. The present study clearly showed that there were prominent species differences between the mouse and rat hippocampus in the CGRP immunoreactivities.