Brain research
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The present study was undertaken to explore the neuronal mechanisms of hypocretin actions on neurons in the nucleus pontis oralis (NPO), a nucleus which plays a key role in the generation of active (REM) sleep. Specifically, we sought to determine whether excitatory postsynaptic potentials (EPSPs) evoked by stimulation of the laterodorsal tegmental nucleus (LDT) and spontaneous EPSPs in NPO neurons are modulated by hypocretin. ⋯ In addition, the frequency and the amplitude of spontaneous EPSPs in NPO neurons increased following hypocretin-1 administration. These data suggest that hypocretinergic processes in the NPO are capable of modulating the activity of NPO neurons that receive excitatory cholinergic inputs from neurons in the LDT.
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Among the numerous pain control mechanisms that have been proposed, those acting at the spinal cord have been broadly studied, but little is known about how neuropeptides originating in supraspinal structures may relate to pain and analgesic mechanisms. Oxytocin (OT), in addition to its well known hormonal action, produces neuronal effects in various regions of the central nervous system. Indeed, some parvocellular neurons in the hypothalamic paraventricular nucleus (PVN) are oxytocinergic and project to the caudal part of the brain and the spinal cord. ⋯ Finally, OT could reduce or partially block the responses to tactile and nociceptive somatic stimulation. We found that spinal cord neurons are sensitive to OT indicating that OT binding sites are functionally active. OT effects suggest the activation of inhibitory interneurons acting on a second order projecting cells to modulate afferent tactile and nociceptive information.
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Effects of intra-medial septum injections of L-arginine, a precursor of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase, and sulpiride, a selective antagonist of dopamine D2 receptor on morphine-induced conditioned place preference (CPP) in male Wistar rats were examined. Using a 3-day schedule of conditioning, morphine (0.5-7.5 mg/kg, s.c.) produced a significant place preference in a dose-dependent manner. The maximum response was observed with 5.0 mg/kg of opioid. ⋯ L-Arginine (0.3-3.0 microg/rat), during conditioning, showed a statistically significant increase in locomotor activity compared with that to control group. Moreover, sulpiride decreased locomotion by itself or in combination with morphine during conditioning and on the test day of morphine CPP. It can be concluded that L-arginine, a precursor of nitric oxide, in the rat median septum may play a role in expression of morphine conditioning due to dopamine release in this area.
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It has recently been demonstrated that valproic acid (VPA) robustly promotes neurite outgrowth, activates the extracellular signal regulated kinase pathway, and increases growth cone-associated protein 43 and bcl-2 levels in cultured human neuroblastoma SH-SY5Y cells. We hypothesized that VPA could also enhance peripheral nerve regeneration in adult animals. ⋯ As measured by sciatic function index and toe spread index, the motor function of the reinnervated hind limbs of rats receiving single axotomy without VPA treatment significantly improved at week 8 and reached plateau levels at about week 11, whereas the motor function of the reinnervated hind limbs of rats receiving single axotomy plus VPA and rats receiving conditional axotomy with or without VPA treatment significantly improved at week 4 and reached plateau levels at about week 8; there was no significant difference of the motor function among the three later groups. The results demonstrated that VPA is able to enhance sciatic nerve regeneration and recovery of motor function in adult rats, suggesting the potential clinical application of VPA for the treatment of peripheral nerve injury in humans.
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The very-high-efficacy, selective 5-HT(1A) receptor agonist, F 13640 produces uniquely powerful analgesia in rat models of chronic pain by novel neuroadaptive mechanisms (inverse tolerance and co-operation with nociception) [Neuropharmacology 43 (2002) 945-958]. A signal transduction theory and evidence suggest that F 13640 initiates these mechanisms, paradoxically, by mimicking the central effects of nociceptive stimulation. We report that the i.p. injection of F 13640 induces c-Fos protein expression in the L3-L5 segments of the spinal cord. ⋯ This parallels literature evidence that c-Fos expression reaches peak late after, and outlasts, nociceptive stimulation. Similar to opioids counteracting noxiously induced c-Fos expression, 10 mg/kg (s.c.) of morphine reduced the number of c-Fos-IR nuclei induced by 0.63 mg/kg of F 13640 (by 45+/-5%; P<0.001). The induction by F 13640 of c-Fos protein expression may relate to the initial hyperalgesia which earlier data indicate the agent to produce early upon its administration.