Brain research
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In this experimental study brief/prolonged and single/repeated, nociceptive stimuli (laser, thermode and electrical) were used to investigate sensory changes in capsaicin-induced primary and secondary hyperalgesia. The pain threshold to prolonged thermode stimulation was reduced in the primary area and remained constant in the secondary area. ⋯ The summation pain threshold to repeated (five stimuli delivered at 0.5, 1, 2 and 3 Hz) laser and electrical stimuli was reduced in the secondary area. The stimulus response functions to single laser and electrical stimuli were increased in the secondary area.
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Prolonged administration of anxiolytic, sedative, and anticonvulsant drugs that act through the GABAA receptor (GABAAR) can evoke tolerance and dependence, suggesting the existence of an endogenous mechanism(s) for altering the ability of such agents to interact with the GABAAR. Uncoupling appears to be one such mechanism. This is a decrease in the allosteric interactions between the benzodiazepine (BZD) recognition site and other agonist or modulator sites on the GABAAR, as measured by potentiation of [3H]flunitrazepam ([3H]FNZ) binding. ⋯ In addition, the EC50 for pregnanolone-induced homologous uncoupling (1.7 microM) is over an order of magnitude greater than that for heterologous uncoupling of GABA and BZD sites (82 nM). Moreover, heterologous uncoupling by pregnanolone is inhibited by the GABA site antagonist SR-95531, whereas homologous uncoupling by pregnanolone is resistant to SR-95531. Therefore, there are at least two distinct ways in which GABAAR modulatory site interactions can be regulated by chronic drug treatment.
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The present experiment was designed to elucidate the characteristics of the response of neurons in the dorsal motor nucleus of the vagus (DMV) to stimulation of the hepatoportal area by hypotonic as well as hypertonic solutions. Responses of 81 neurons that exhibited an antidromic response to electrical stimulation of the ventral gastric vagus were recorded in the left DMV in urethane-chloralose anesthetized rats. The effects on these 81 neurons of portal infusion of hypertonic saline (3.6% NaCl) and of pure water were examined. ⋯ Therefore, the responses to portal infusion of water appear to be derived from activation of the hepatoportal receptors. These results indicate that a certain fraction of DMV neurons respond similarly to portal infusions of hypertonic and hypotonic saline. It is possible that there exist some reflex arcs that mediate a similar response to both an increase and a decrease in portal blood osmolarity (or Na+ concentration), namely, a suppression of absorption.
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Pituitary adenylate cyclase-activating polypeptide (PACAP) has recently been demonstrated in sensory neurons. In the present study on rat 17.5% of all neurons, mainly of small size, contained PACAP in normal dorsal root ganglia (DRGs). Transection of the sciatic nerve induced a rapid and strong upregulation in PACAP peptide and mRNA levels which could be seen already after 15 h. ⋯ Also a moderate increase (about 20%) in PACAP levels was found in the superficial spinal dorsal horn 3 days after nerve transection. Taken together, our results suggest that PACAP is involved in the response to nerve injury. The very high levels of expression in different populations of DRG neurons after axotomy, and its different time course as compared to galanin, NPY and VIP indicate that it may play a complementary and/or different role than these peptides in the adaptation to nerve injury, especially in its early phase.
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The efficacy of L-dihydroxyphenylalanine (L-DOPA) in ameliorating the symptoms of Parkinson's disease (PD) is attributed to its conversion to dopamine (DA) by the enzyme aromatic L-amino-acid decarboxylase (AADC) in the striatum. Although the site of this conversion in the DA-denervated striatum has yet to be identified, it has been proposed that L-DOPA could be converted to DA at non-dopaminergic sites containing AADC. In the present study, we used immunocytochemical techniques to examine the localization of AADC and DA in the striatum of rats with a unilateral 6-hydroxydopamine (6-OHDA) lesion of the nigrostriatal dopaminergic projection. ⋯ These results strongly suggest the existence of a class of AADC-containing striatal cells that can form DA from exogenous L-DOPA in the rat. In the DA deafferented striatum, DA produced by these cells from exogenous L-DOPA could be released to exert physiological effects on DA receptive tissue. It is possible that similar cells could contribute to the efficacy of L-DOPA in the treatment of Parkinson's disease.