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Chronic Pretreatment (chronic + pretreatment)
Selected AbstractsNeurochemical regulation of swallowing reflex in guinea pigsGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1-2 2001Yu X Jia Background: Most peripheral afferent fibers involved in swallowing travel through the glossopharyngeal and vagus nerves and terminate in the nucleus of the tractus solitarius (NTS) and nodose ganglion (NG). Sensory neurons within the NTS and NG contain several neurotransmitters, including acetylcholine, histamine, serotonin and dopamine. The roles of these four neurotransmitters were investigated. Methods: The effects of atropine (muscarinic cholinergic receptor antagonist); pyrilamine maleate (PM, histamine H1 receptor antagonist); cimetidine (histamine H2 receptor antagonist); 8-hydroxy-2-(di- n -propylamino)-tetralin (8-OH-DPAT, specific 5-HT1A receptor agonist); and selective dopamine D1 receptor antagonist (Sch-23390) on the number of swallows elicited by distilled water in anesthetized guinea pigs were investigated. Results: Atropine (0.2 mg/kg) inhibited swallowing by approximately 70%; PM (30 mg/kg) inhibited swallowing by approximately 60%; cimetidine (30 mg/kg) inhibited swallowing by approximately 52.9% and Sch-23390 (chronic treatment) inhibited swallowing by approximately 40%. In contrast, 8-OH-DPAT did not alter the number of swallows. Chronic pretreatment of Sch-23390 markedly decreased the substance P (SP) content in the pharyngeal mucosa and the esophagus. Conclusion: These findings indicate that acetylcholine, histamine and dopamine are involved in the regulation of the swallowing reflex, whereas it is unlikely that serotonin is involved. [source] Downregulation of tonic GABA currents following epileptogenic stimulation of rat hippocampal culturesTHE JOURNAL OF PHYSIOLOGY, Issue 2 2006Jin-shun Qi Deficits in GABAergic inhibitory transmission are a hallmark of temporal lobe epilepsy and have been replicated in animal and tissue culture models of epilepsy. GABAergic inhibition comprises phasic and tonic inhibition that is mediated by synaptic and extrasynaptic GABAA receptors, respectively. We have recently demonstrated that chronic stimulation with cyclothiazide (CTZ) or kainic acid (KA) induces robust epileptiform activity in hippocampal neurons both in vitro and in vivo. Here, we report a downregulation of tonic GABA inhibition after chronic epileptogenic stimulation of rat hippocampal cultures. Chronic pretreatment of hippocampal neurons with CTZ or KA resulted in a marked reduction in GABAergic inhibition, as shown by a significant decrease in whole-cell GABA currents and in the frequency of miniature inhibitory postsynaptic currents (mIPSCs). Interestingly, synaptically localized GABAA receptors remained relatively stable, as evidenced by the unaltered amplitude of mIPSCs, as well as the unchanged punctate immunoreactivity of ,2 subunit-containing postsynaptic GABAA receptors. In contrast, tonic GABA currents, assessed either by a GABAA receptor antagonist bicuculline or a selective extrasynaptic GABAA receptor agonist THIP, were significantly reduced following epileptogenic stimulation. These results reveal a novel form of neural plasticity, that epileptogenic stimulation can selectively downregulate extrasynaptic GABAA receptors while leaving synaptic GABAA receptors unchanged. Thus, in addition to synaptic alteration of GABAergic transmission, regulation of tonic inhibition may also play an important role during epileptogenesis. [source] The effect of tamoxifen on the pharmacokinetics of letrozole in female ratsBIOPHARMACEUTICS AND DRUG DISPOSITION, Issue 7 2006X. Tao Abstract The effects of single doses of tamoxifen (TAM; 0.5,5 mg/kg, i.v.) and chronic pretreatment with TAM (0.1,5.0 mg/kg/day, i.p. for 7 consecutive days) on letrozole (0.5 mg/kg, i.v.) pharmacokinetics were evaluated in female Sprague-Dawley rats. The plasma concentration-time profiles of letrozole (0.1,2.0 mg/kg) after single i.v. doses were analysed by the non-compartment model with terminal half-lives (t1/2,,z) ranging from 34.3 to 37.5 h. The volume of distribution at the terminal phases (Vd(,z)) ranged from 1.9 to 2.1 l/kg and clearance (CL) varied from 0.036 to 0.042 l/(h·kg). After co-administration of TAM and letrozole intravenously, the t1/2, Vd(,z) and CL of letrozole were not significantly altered. Chronic pretreatment with TAM significantly decreased the t1/2 of letrozole by about 33%, and increased its clearance by an average of 40%. However, TAM pretreatment did not significantly affect the Vd((,z) of letrozole in female rats. Co-administration of letrozole and TAM orally increased the absorption half-life of letrozole threefold although the absolute bioavailability remained unchanged. These observations suggest that single oral doses of TAM delay the absorption of letrozole while chronic pretreatment with TAM accelerates the elimination of letrozole, probably due to induction of cytochrome P450 enzymes in rats. Copyright © 2006 John Wiley & Sons, Ltd. [source] | ||||||||||