Brain research
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Comparative Study
Differential antinociception by morphine and methadone in two sub-strains of Sprague-Dawley rats and its potentiation by dextromethorphan.
The antinociceptive effect of morphine and methadone was tested in two substrains of Sprague-Dawley (SD) rats, from B&K Universal, Sweden (BK) and Mollegård, Denmark (DK). In both sub-strains of SD rats subcutaneous morphine or methadone produced dose-dependent antinociception on the hot plate test. However, the effect of the opioids was less in DK-SD than BK-SD rats, particularly for morphine as it failed to produce maximal antinociception even at high doses. ⋯ The potentiation of morphine by dextromethorphan was significantly greater than its effect on methadone at equipotent doses. The results showed that there is a sub-strain difference for SD rats in the response to the antinociceptive effect of opioids, which may be due to greater NMDA receptor activity in DK-SD than in BK-SD rats. The higher efficacy of methadone may be derived from its proposed NMDA receptor blocking property and/or high intrinsic activity.
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The inhibitory effects of opioids on voltage-dependent calcium channels (VDCCs) were investigated in cultured porcine adrenal chromaffin cells using whole-cell patch clamp technique. The effects of the opioid on [Ca(2+)](i) increase and catecholamine secretion induced by high K(+) were also examined in single cells by fura-2 microfluorimetry and amperometry. A depolarizing pulse to 0 mV (test pulse) from a holding potential of -80 mV evoked an inward barium current (I(Ba)), which was reversibly inhibited by methionine-enkephalin. ⋯ DAMGO reversibly inhibited the [Ca(2+)](i) increase and catecholamine release induced by high K(+). RT-PCR revealed the expression of mu-, delta- and kappa-opioid receptor mRNAs in cultured adrenal chromaffin cells. These results suggest that porcine adrenal chromaffin cells possess mu-, delta- and kappa-opioid receptors and activation of opioid receptors mainly inhibits N-type VDCCs via pertussis toxin-sensitive G-proteins.
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Perinatal brain injuries and the subsequent development of cerebral palsy are closely associated with intrauterine infections and inflammatory response. Antibiotics have proven futile in reducing perinatal brain injuries. We tested whether treatment with the anti-inflammatory cytokine IL-10 could have beneficial effects during a concomitant endotoxin and cerebral hypoxic-ischemic challenge. Thirty-three newborn piglets were randomized to pretreatment with: ⋯ placebo, Endotoxin: 2 kU/kg bolus and infusion of 1 kU/kg per h of endotoxin, or Endotoxin+IL-10: endotoxin in addition to 50 microg/kg of porcine recombinant IL-10. We induced cerebral hypoxia-ischemia by bilateral clamping of the common carotid arteries and ventilation with 8% oxygen for 20 min followed by 3 h of reoxygenation/reperfusion. Extracellular lactate, pyruvate, glycerol and glutamate, microcirculation and tissue oxygenation were monitored in the striatum by microdialysis, laser Doppler flow and oxygen tension probe, respectively. During and/or after cerebral hypoxia-ischemia, Endotoxin caused marked deterioration of the cerebral metabolic situation with higher lactate/pyruvate ratio (P=0.003), compared to CONTROLS and Endotoxin+IL-10. This was caused mainly by very low levels of pyruvate (P=0.001). During the following reoxygenation, Endotoxin compromised cerebral microcirculation (P=0.038) and tissue oxygenation (P=0.012) compared to CONTROLS and Endotoxin+IL-10. After a period of remission, a secondary energy failure and a new rise in the lactate/pyruvate ratio was seen in Endotoxin (P=0.002), but not in CONTROLS or Endotoxin+IL-10. At the end of observation, only the Endotoxin+IL-10 group had regained their baseline values in all variables. Thus IL-10 counteracts acute effects of endotoxin on cerebral metabolism, microcirculation and oxygen tension during hypoxia-ischemia in the perinatal brain.
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Two brain-specific proteins, S-100beta and neuron-specific enolase (NSE), are released systemically after cerebral lesions, but S-100beta levels sometimes rise in the absence of neuronal damage. We hypothesized that S-100beta is a marker of blood-brain barrier (BBB) leakage rather than of neuronal damage. ⋯ Serum S-100beta increased significantly after mannitol infusion (P<0.05) while NSE did not. This suggests that S-100beta is an early marker of BBB opening that is not necessarily related to neuronal damage.