Brain research
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The present study was undertaken to investigate and compare the properties of noradrenaline release in the locus coeruleus (LC) and prefrontal cortex (PFC). For that aim the dual-probe microdialysis technique was applied for simultaneous detection of noradrenaline levels in the LC and PFC in conscious rats. Calcium omission in the LC decreased noradrenaline levels in the LC, but increased its levels in the PFC. ⋯ When the GABA(A) antagonist bicuculline was applied to the LC, noradrenaline increased in the LC as well as in the PFC. It is concluded that the release of noradrenaline from somatodendritic sites and nerve terminals responded in a similar manner to presynaptic receptor modulation. The possible existence of dendritic noradrenaline release is discussed.
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Comparative Study
Differential impact of predator or immobilization stressors on central corticotropin-releasing hormone and bombesin-like peptides in Fast and Slow seizing rat.
Lines of rats selectively bred for amygdala excitability, as reflected by kindling rates in response to electrical stimulation, also exhibit differences in tests of anxiety. Inasmuch as corticotropin-releasing hormone (CRH) and bombesin (BN) have been associated with anxiety, regional levels and release of these peptides, as well as plasma adrenocorticotropic hormone (ACTH) and corticosterone, were assessed in 'Slow' and 'Fast' seizing rats following predator exposure (ferret) or immobilization. Ferret exposure elicited a greater increase of plasma ACTH and corticosterone concentrations in the Slow than in the Fast rats. ⋯ In vivo microdialysis experiments revealed that in response to ferret exposure, the Slow rats showed a greater CRH release at the central nucleus of the amygdala (CeA) as compared to Fast rats. However, immobilization elicited a more pronounced release of CRH in Fast than in Slow rats. Taken together, the results demonstrate that these two lines of rats show differential endocrinological and neurochemical response patterns to these stressors.
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Bone morphogenetic protein-7 (BMP-7) has been shown to enhance dendritic growth and improve functional recovery after experimental stroke. In this study, we examined the effect of BMP-7 on functional recovery, local cerebral blood flow (LCBF) and local cerebral glucose utilization (LCMRglu) following transient middle cerebral artery occlusion. Sprague--Dawley rats (n=29) were anesthetized with halothane/nitrous oxide and received 2-h middle cerebral artery occlusion (MCAo) by poly-L-lysine-coated intraluminal suture. ⋯ Rectal and cranial temperatures, mean blood pressure, plasma glucose and blood gases were similar among groups. BMP-7 significantly improved the total neurological score compared to vehicle at 48 h after MCAo (7.3+/-0.4 vs. 9.0+/-0.2, respectively; P<0.0003). Compared to vehicle-rats, BMP-7 enhanced glucose utilization in the basal ganglia ipsilateral to stroke and improved LCBF in ipsilateral subthalamus, but decreased LCBF and LCMRglu in contralateral cortical regions.
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Nociceptin or orphanin FQ (N/OFQ) is the natural ligand of the opioid receptor-like 1 receptor (ORL-1), which has been also classified as the fourth member of the opioid family of receptors and named OP(4). Elucidation of the biological role of N/OFQ has been hampered by the lack of compounds that selectively block the OP(4) receptor. Recently, a N/OFQ derivative, [Nphe(1)]N/OFQ(1-13)NH(2), has been found to possess OP(4) antagonistic properties both in vitro and in vivo models. ⋯ Intrathecal (i.t.) administration of N/OFQ (0.2--20 nmoles) dose-dependently reversed mechanical allodynic-like behavior, while [Nphe(1)]N/OFQ(1-13)NH(2) (20--120 nmoles, i.t.) was ineffective on its own. [Nphe(1)]N/OFQ(1-13)NH(2) (60--120 nmoles, i.t.) antagonized N/OFQ (about 80% of reduction) but did not modify the activity of morphine (20 nmoles, i.t.). These results further support, for the first time in a chronic model of pain, the specific antagonistic profile of [Nphe(1)]N/OFQ(1-13)NH(2)vs the OP(4) receptor. This pseudopeptide is an interesting pharmacological tool to better clarify the role of N/OFQ in pathophysiology.
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Comparative Study
Neuroprotection of S(+) ketamine isomer in global forebrain ischemia.
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist ketamine can block the action of excitotoxic amino acids in the central nervous system. S(+) ketamine has a 2-3 times higher anesthetic potency compared with the ketamine-racemate and also shows a higher neuroprotective efficacy in vitro. To determine the neuroprotective activity of S(+) ketamine compared with its R(-) stereoisomer in vivo, we examined the functional and neurohistological outcome in rats treated 15 min after global forebrain ischemia with S(+) ketamine in different dosages compared with R(-) ketamine. ⋯ No significant neuroprotection was observed in the hippocampus. Although no significant change in rCBF was found, S(+) ketamine restored the cortical HbO2 to preischemic values. These results indicate that S(+) ketamine in higher dosages can reduce neuronal damage in the cortex after cerebral ischemia, possibly by improving the ratio of oxygen supply to consumption in the postischemic tissue.