Neuropharmacology
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The aim of the current study was to investigate the role of the rostroventromedial medulla (RVM) in alpha 2-adrenoceptor-mediated antinociception. Medetomidine or clonidine, selective alpha 2-adrenoceptor agonists were microinjected into the RVM in unanesthetized rats with a chronic guide cannula. The antinociceptive effects were evaluated using the tail-flick and hot-plate tests. ⋯ Microinjections of medetomidine into the cerebellum or the PAG produced an identical dose-response curve in the tail-flick test as that obtained following microinjection into the RVM. In spinalized rats the antinociceptive effect (tail-flick test) induced by medetomidine microinjected into the RVM was not less effective than in intact rats. Lidocaine (5%) or atipamezole (5 micrograms) microinjected into the RVM did not attenuate the antinociception induced by systemically administered medetomidine (100 micrograms/kg, s.c.).(ABSTRACT TRUNCATED AT 250 WORDS)
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Dose-responsive motor activity induced by systemic injection of the kappa (kappa) preferring opioid agonist, U50,488H (1-10 mg/kg, s.c.) in guinea pigs was recently reported [Brent P. J. and Bot G. (1992) Psychopharmacology 107: 581-590], characterised at the higher doses used (5-10 mg/kg) by sustained postural abnormalities. The effects on the U50,488H-induced, abnormal, motor response of pharmacological manipulation of opioid receptors and sigma (sigma) sites was studied. ⋯ In addition, haloperidol (1 and 5 mg/kg, s.c.), dextromethorphan (10 mg/kg, s.c.) and DTG (30 mg/kg, s.c.), given in combination with U50,488H, induced behaviour characterised by marked oral activity. In contrast to the effect of haloperidol, pretreatment with the selective dopamine D-2 antagonist, raclopride (10 mg/kg, s.c.), had no significant effect on the abnormal movements induced by U50,488H, but did induce oral activity. These data indicate the possible involvement of kappa opioid receptors in the abnormal movement induced by U50,488H, and further demonstrate that there is an interaction between the kappa receptors and sigma sites which can influence the abnormal motor activity.
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This study tested the hypothesis that local cerebral O2 supply and consumption are not precisely balanced and that vascular alpha adrenoceptors affect this equilibrium. Twenty-two male Long-Evans rats were used in this study. Cerebral blood flow was determined in six regions, using 4-iodo [N-methyl-14C]antipyrine. ⋯ The average value increased slightly but significantly to 62 +/- 8%. Thus, N-methyl chlorpromazine eliminated many microregions of high O2 extraction. This indicated that vascular alpha adrenoceptors limit cerebral blood flow to some of the brain regions.
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The cardiovascular effects of central administration of cholinomimetics were investigated in anesthetized cats, to identify the site and mechanism of their action. Physostigmine, 10-100 micrograms, given by intracerebroventricular administration (i.c.v.) caused a dose-dependent reduction in blood pressure and renal sympathetic nerve discharges and no change in heart rate, which were antagonized by intravenous injection (i.v.) of atropine but not by methscopolamine or pirenzepine, given intravenously. Carbachol 3-30 micrograms (i.c.v.) reduced blood pressure and renal sympathetic nerve discharges and caused no change in heart rate. ⋯ Under pretreatment with atropine into the ventral medulla but not pirenzepine, physostigmine, given intravenously, did not influence blood pressure. It is concluded that a cholinergic mechanism, concerned with a depressor response, is located on the ventral medulla. Muscarinic receptors of the non-M1 subtype, possibly M2, are related to this mechanism.
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Dexmedetomedine is a potent alpha 2 adrenergic agonist which can reduce anesthetic requirements by over 90% in rats and dogs. This study examined the effects of various doses of dexmedetomidine on the following monitored variables in New Zealand white rabbits: arterial blood gases, mean arterial pressure, respiratory rate, heart rate, and level of sedation. Following the percutaneous insertion of arterial and venous catheters, 21 rabbits received an infusion of saline or dexmedetomidine (20, 80 or 320 micrograms/kg). ⋯ To examine the ability of an alpha 2 adrenergic antagonist to reverse the effects of dexmedetomidine, 5 rabbits initially received 320 micrograms/kg of dexmedetomidine as described above. Seven minutes after completion of the infusion, 900 micrograms/kg of the alpha 2 adrenergic antagonist, idazoxan, was administered. This resulted in a prompt and sustained reversal of the hypercarbia and sedation produced by the dexmedetomidine.