Neuroscience
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The role of peripheral serotonin (5HT) 2A and 5HT1A receptors on the orofacial nocifensive behavioral activities evoked by the injection of formalin into the masseter muscle was evaluated in the rats with persistent temporomandibular joint (TMJ) inflammation evoked by Complete Freund's Adjuvant (CFA). The orofacial nocifensive behavioral activities evoked by the injection of formalin into masseter muscle were significantly enhanced at 1 day (CFA day 1 group) or 7 days (CFA day 7 group) during TMJ inflammation. ⋯ Moreover, local administration of ketanserin (0.1 mg) or propranolol (0.1 mg) into masseter muscle did not inhibit nocifensive orofacial behavior in rats without TMJ inflammation. These data suggest that persistent TMJ inflammation causes the elevation of the orofacial nocifensive behavior, and peripheral 5HT2A receptors play an important role in mediating the deep craniofacial tissue nociception in rats with TMJ inflammation.
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It has been well documented that the activation of c-Jun N-terminal protein kinase (JNK) pathway and caspase-3 signal are involved in the delayed neuronal cell death in cerebral ischemia. In this study, we first detected the activation pattern of JNK signaling including mixed lineage kinase (MLK)3, mitogen-activated protein kinase kinase (MKK)7 and JNK3 in hippocampal CA1 and CA3/DG regions at various time points after 15 min of ischemia. These results indicated that cerebral ischemia induced the continuous activation of MLK3/MKK7/JNK3 cascade, which all had two active waves only in the CA1 region. ⋯ Additionally, pretreatment of K252a significantly increased the number of the surviving CA1 pyramidal cells at 5 days of reperfusion. Our results suggest that K252a play a neuroprotective role in ischemic injury via inhibition of the JNK pathway, involving the death effector of caspase-3. Thus, JNK signaling may eventually emerge as a prime target for novel therapeutic approaches to treatment of ischemic stroke, and K252a may serve as a potential and important neuroprotectant in therapeutic aspect in ischemic stroke.
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These experiments explore the role of 5-HT1A receptors in the regulation of cell proliferation in the dentate gyrus of the intact and adrenalectomized adult rat. Depleting 5-HT with p-chlorophenylalanine (300 mg/kg initially followed by 100 mg/kg/day) or stimulating 5-HT1A receptors with 8-OH-DPAT (1 mg/kg or 2 mg/kg, s.c. injections twice daily) for 14 days had no effect on cell proliferation as measured by Ki-67 or BrdU (5-bromo-3-deoxyuridine) immunocytochemistry in the dentate gyrus. However, combined treatment with p-chlorophenylalanine followed by 8-OH-DPAT significantly increased cell proliferation compared with p-chlorophenylalanine alone. ⋯ The 5-HT1A antagonist WAY-100635 (1.5 mg/kg/day also delivered by osmotic pump) by itself did not alter cell proliferation, confirming that reduced serotonin activity does not change proliferation, but blocked the effect of 8-OH-DPAT. However, WAY-100635 could not block the stimulating action of adrenalectomy cell proliferation. 5-HT1A mRNA expression was not altered in the hippocampus by adrenalectomy. Thus, the effect of adrenalectomy on cell proliferation and survival is not 5-HT1A dependent, despite the interaction between 5-HT1A and corticosterone.
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Chronic treatment with the selective serotonin reuptake inhibitor paroxetine impairs the functioning of 5-HT(1A) receptors involved in ejaculation. This could underlie the development of delayed ejaculation often reported by men treated with paroxetine. The neurobiological substrate linking the effects of selective serotonin reuptake inhibitor-treatment and 5-HT(1A) receptor activation with ejaculation was investigated. ⋯ Chronic treatment with paroxetine reduced Fos-immunoreactivity in the locus coeruleus, and prevented the increase in Fos-immunoreactive neurons induced by 8-OH-DPAT in the oxytocinergic magnocellular part of the paraventricular nucleus as well as in the locus coeruleus. Since oxytocin and noradrenalin facilitate ejaculation, the alterations in Fos-IR in these areas could connect selective serotonin reuptake inhibitor treatment and 5-HT(1A) receptor activation to ejaculation. Chronic paroxetine treatment and 8-OH-DPAT changed c-fos expression in a number of other brain areas, indicating that Fos-immunohistochemistry is a useful tool to find locations where selective serotonin reuptake inhibitors and 8-OH-DPAT exert their effects.
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The present studies aimed to determine whether cocaine- and amphetamine-regulated transcript (CART) peptide in the nucleus of accumbens shell (AcbSh) is implicated in the regulation of food intake. Bilateral intranuclear injections of CART peptide (55-102, 1 microg/microl/side) into the AcbSh decreased food intake with no change in locomotion activity and attenuated the orexigenic effect of the GABA(A) agonist muscimol (100 ng/microl/side) in male Sprague-Dawley rats. Decreased food intake after bilateral intranuclear injections of CART was more sustained in freely fed rats than in food-deprived rats, suggesting fuel availability is an important factor in modulating the function of CART in the regulation of feeding. ⋯ Moreover, many of these efferent cells contain CART immunoreactivity, including those which reside within the AcbSh, suggesting that accumbal CART circuitry is involved in the central function of the nucleus accumbens. Furthermore, fasting suppressed CART mRNA levels in the AcbSh, paraventricular nucleus of the hypothalamus, arcuate nucleus, and the perifornical region, indicating that the Acb is sensitive to fuel availability to an extent similar to those regions in the hypothalamus. Our findings are the first to demonstrate that CART mRNA in the AcbSh is sensitive to metabolic challenges and that injection of CART peptide into the AcbSh has an inhibitory effect on food intake.