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PubMed1983

Theta rhythm related hippocampal cell discharges in the urethane anaesthetized rat: evidence for a predominant entorhinal input.

Unit spike activity and slow wave field potentials were recorded in the CA1 pyramidal layer and the dentate granular layer of the dorsal hippocampus of urethane anaesthetized rats during theta rhythm. 70% of the units in the pyramidal layer and all units in the granular layer, having a discharge pattern related to theta rhythm, had their mean moment of discharge in the positive phase of the theta wave recorded in the pyramidal layer. Combined with the results of a modelling study (Holsheimer et al. 1982) it appears that in rat under urethane the theta modulated input to the CA1 pyramidal cells and the dentate granular cells will be mediated predominantly by pathways which terminate distally at these cells: the perforant path.

Action Potentials↗
PubMed1992

Evidence for different neurochemical contributions to long-term potentiation and to kindling and kindling-induced potentiation: role of NMDA and urethane-sensitive mechanisms.

Long-term potentiation (LTP) and kindling share a number of features, and it has been suggested that LTP might constitute the cellular mechanism of kindling. This question was approached by assessing the effect of urethane anesthesia (0.75 or 1.5 g/kg) or blockade of NMDA receptors by local infusion of DL-2-amino-5-phosphonovaleric acid (APV; 7.5 micrograms) on LTP, partial kindling, and kindling-induced potentiation (KIP) in the perforant path-dentate gyrus circuit of the intact hooded rat. Urethane anesthesia attenuated but did not block LTP and completely blocked partial kindling and KIP. APV completely blocked LTP but did not block partial kindling or KIP in the unanesthetized rat. These results suggest that different neurochemical mechanisms can support LTP on the one hand, and kindling and KIP on the other. They are consistent with a contribution by NMDA-mediated LTP to kindling and KIP, but they indicate that this contribution is not crucial for kindling and KIP in this circuit.

2-Amino-5-phosphonovalerate↗
PubMed1988

Excitation of striatal neurons by dexamphetamine is not abolished by either chloral hydrate or urethane anaesthesia.

In order to understand differences between studies maintaining that dopamine actions are significantly reduced as a result of chloral hydrate anaesthesia or not affected to any appreciable extent, striatal neuronal responses to the indirect dopamine agonist, dexamphetamine, were examined in rats anaesthetized with either chloral hydrate (400 mg/kg) or urethane (1.5 g/kg). Striatal neuronal activity was markedly depressed by chloral hydrate and urethane. However, striatal neurons still responded to 2.5 mg/kg dexamphetamine with marked excitation. These results indirectly support earlier iontophoretic studies on the excitatory action of dopamine on striatal neurons in chloral hydrate-anaesthetized animals. Furthermore, the ability of dexamphetamine, primarily an indirect dopamine agonist, to excite striatal neurons in these anaesthetized animals suggests that stimulation of both D1 and D2 receptors is not abolished by anaesthesia.

Anesthesia↗
PubMed1991

Simultaneous recording of vesical and urethral pressure in urethane-anesthetized rats: effect of neuromuscular blocking agents on the activity of the external urethral sphincter.

In urethane-anesthetized rats we made a disconnection of the urinary bladder from the urethra and performed a simultaneous recording of the vesical and external urethral sphincter (EUS) pressures. Throughout the collecting phase, the EUS pressure was higher than that recorded into the bladder. Gallamine (10 mg/kg i.v.) or d-tubocurarine (100 micrograms/kg i.v.), did not alter the value of intraurethral pressure. When a reflex bladder contraction occurred in response to filling (expulsion phase) the intravesical pressure exceeded the urethral pressure and at the top of the vesical contraction a series of rapid intraluminal pressure high frequency oscillations (IPHFO) were recorded at the urethral recording site, which were abolished by neuromuscular blocking agents as well as after acute sectioning of pudendal nerves. IPHFO was still present in rats in which the periurethral muscles (pelvic floor), have been precedently dissected. To get further information about the physiological consequence of the EUS functional impairment induced by neuromuscular blocking agents, we used the non-stop transvesical cystometrogram. In these conditions, blockade of the EUS did not produce passive urine dripping during the filling phase, but absence of the rhythmic striated urethral activity during the vesical expulsion phase produced a significant increase of the residual volume from 35% (control) to 75%. We present an original pharmacological method in a species whose small dimensions create technical problems for recording pressure signals from the lower urinary tract. Moreover, we have gained information on the origin of the IPHFOs and about the role of the EUS during the collecting and the expulsion phase of the voiding cycle in urethane anesthetized rats.

Animals↗
PubMed1990

Activity of urethane and N,N-dimethylurethane in the mouse bone-marrow micronucleus assay: equivalence of oral and intraperitoneal routes of exposure.

Urethane is shown to be active in the mouse bone-marrow micronucleus assay when administered as a single dose by either gavage or intraperitoneal injection. The magnitude of the response using the two routes was not statistically significantly different. N,N-Dimethylurethane (DMU) is shown to be mutagenic to Salmonella and active in the bone-marrow micronucleus assay by both routes of administration. The activity of DMU in the bone marrow precludes elimination of ethanol, yielding cyanate ion, as an explanation for the micronucleus-inducing activity of urethane.

Administration, Oral↗
PubMed1991

Rapid changes in the content of proenkephalin A and corticotrophin releasing hormone mRNAs in the paraventricular nucleus during morphine withdrawal in urethane-anaesthetized rats.

Quantitative in situ hybridization was used to measure corticotrophin-releasing hormone (CRH) and proenkephalin A mRNA in the medial parvocellular paraventricular nucleus (PVN) 4 h after test procedures. Urethane anaesthesia alone resulted in a significant increase in both CRH and proenkephalin transcripts. The additional stimulus of i.p. hypertonic saline, however, resulted in a further significant increase in both mRNA species. Female rats were given intracerebroventricular (i.c.v.) infusion for 5 days of either morphine sulphate to induce tolerance and dependence, or vehicle, via a subcutaneous osmotic minipump implanted under ether anaesthesia. The rats were then anaesthetized with urethane, fitted with an intravenous cannula for injections and 65 min later either naloxone (5 mg/kg) or vehicle was injected. Naloxone alone in the i.c.v. vehicle rats had no effect on CRH or proenkephalin A mRNA. In i.c.v. morphine-infused rats proenkephalin a mRNA in the PVN was significantly less than in controls. Naloxone given to i.c.v. morphine-infused rats resulted in a doubling of hybridization to proenkephalin mRNA in the PVN which was significantly greater than that seen in the i.c.v. vehicle group. CRH mRNA in the PVN was not altered either by naloxone in control rats, or by chronic i.c.v. morphine infusion. By contrast, naloxone did increase CRH mRNA by ca. 40% in morphine-infused rats. The results show that stress-induced increases in CRH and enkephalin mRNAs in the PVN do not require conscious appreciation of the stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia, General↗
PubMed1988

Reconstruction after hemimandibulectomy using a costochondral rib graft and a dacron-urethane tray with autogenous iliac bone: report of a case.

A case is presented that describes a method of mandibular reconstruction using a costochondral graft for replacement of the condyle that is attached to a dacron-urethane tray filled with particulate bone and marrow harvested from the ilium and secured to the distal mandibular segment with stainless steel wire. The requirements of graft immobilization and early return to function were met by initially using maxillomandibular fixation and then using external pin fixation with a small hinge incorporated into the acrylic bar. The advantages of using a dacron-urethane tray as opposed to a metallic tray are described, and the use of costochondral grafts is reviewed.

Adult↗
PubMed1986

Inhibition of urethan-induced lung tumors in mice by dietary N-acetylcysteine.

The thiol N-acetylcysteine (NAC), a precursor of intracellular glutathione (GSH), efficiently prevented the induction of lung tumors in Swiss albino mice, when supplemented to the diet (0.2%) both before and after an i.p. injection of the carcinogen urethan (ethyl carbamate). Irrespective of urethan administration, NAC also significantly enhanced GSH S-transferase activity in liver preparations of the same animals. These data show that, under certain conditions, it is possible to prevent chemically induced cancer by increasing the levels of physiological trapping agents.

Acetylcysteine↗
PubMed1988

Effects of chloralose-urethane anesthesia on single-axon reciprocal Ia IPSPs in the cat.

Reciprocal Ia inhibitory postsynaptic potentials (IPSPs) generated by single afferents have been recorded with signal averaging in unanesthetized ischemic-decapitate cats for comparison with measurements previously obtained from preparations anesthetized with a mixture of chloralose and urethane. The results are similar to those which we obtained recently for single-axon recurrent IPSPs. Together, the studies show that chloralose-urethane anesthesia has a depressant effect on two widely studied circuits in the mammalian spinal cord.

Anesthesia↗
PubMed1995

Sexually dimorphic perforant path long-term potentiation (LTP) in urethane-anesthetized rats.

Sex differences in perforant path long-term potentiation (LTP) have been reported in pentobarbital-anesthetized rats. Because this effect may be due to the prominent sex difference in barbiturate sensitivity, the present report examined perforant path-dentate granule cell synaptic transmission and long-term potentiation (LTP) in adult male and female rats anesthetized with urethane. Spectral analysis of hippocampal electroencephalographic (EEG) activity indicated that urethane induced similar levels of anesthesia in male and female rats, and there were no sex differences in the latency or amplitude of extracellular field potentials evoked in the dentate gyrus following perforant path stimulation. In contrast, there was a robust sex difference in the magnitude of LTP induced in the dentate gyrus following high-frequency stimulation (HFS) of the perforant path. This sex difference in LTP was paralleled by a sex difference in the magnitude of N-methyl-D-aspartate (NMDA) receptor activation generated by perforant path HFS. These results demonstrate a sex difference in hippocampal LTP that cannot be explained by a sex difference in level of anesthesia.

Analysis of Variance↗
PubMed1988

Propagated motor activity in the small intestine of urethane-anaesthetized rats: inhibitory action of sympathetic and capsaicin-sensitive nerves.

1. In the duodenum/small intestine of urethane-anesthetized rats, a series of atropine- and hexamethonium-sensitive phasic contractions activity were recorded by using a balloon. With two balloons, one in the proximal duodenum (B1) and the other at a distal site (B2) a co-ordinated motor activity was observed which migrated from B1 to B2. 2. Spontaneous activity of the duodenum was greater in either adrenalectomized, guanethidine- or capsaicin-pretreated than in control rats. In guanethidine-pretreated animals a series of atropine-resistant but hexamethonium-resistant rhythmic contractions could be demonstrated. 3. In control rats, distension of the balloon produced an inhibitory effect on rhythmic contractions which were ultimately suppressed. Distension had little inhibitory effect on duodenal motor activity of adrenalectomized, guanethidine- or capsaicin-pretreated rats. 4. These findings indicate that the propagated motor activity in the duodenum/small intestine of urethane anesthetized rats can be modulated by the adrenals as well as sympathetic and capsaicin-sensitive nerves.

Adrenalectomy↗
PubMed1992

Effect of urethane on hydralazine-induced tachycardia in rats.

1. In conscious normotensive rats, hydralazine (5-10 mg kg-1 p.o.) produced a dose-related fall in systolic blood pressure, accompanied by a pronounced increase in heart rate. 2. The tachycardia induced by hydralazine (10 mg kg-1 p.o.) in conscious normotensive rats was strongly inhibited after anaesthesia with urethane (1.26 g kg-1 i.p.). 3. In anaesthetized normotensive rats, hydralazine (1 mg kg-1 i.v.) caused a fall in mean blood pressure, accompanied by irregular effects on the heart rate that consisted in a combination of initial tachycardia followed by bradycardia. 4. In pithed rats, hydralazine (1 mg kg-1 i.v.) did not affect mean arterial blood pressure but produced a significant decrease in heart rate. 5. In rat isolated atria, hydralazine (2 mM) produced a positive inotropic/negative chronotropic effect. 6. These results suggest that urethane inhibits the cardiovascular reflex that causes the tachycardia induced by hydralazine in conscious normotensive rats. For this reason, in anaesthetized normotensive rats appear the direct effect of the drug on the heart.

Anesthesia↗
PubMed1989

Action of urethane on dorsal lateral geniculate neurons.

Light evoked neuronal responses of urethane anaesthetized rats were compared with those recorded in freely moving animals. The results demonstrate that urethane reduces the firing frequency, the response probability as well as the number of excitatory light evoked response phases. These changes are combined with a prolongation of the postexcitatory inhibitory phases. The latencies to diffuse flashes are increased in geniculate neuronal responses as well as in evoked potentials recorded from the visual cortex. A similar relation exists between diminution of late geniculate excitations and suppression of cortical photic afterdischarges.

Action Potentials↗
PubMed1990

Conditioning-related changes of unit activity in the dorsal lateral geniculate nucleus of urethane-anaesthetized rats.

Changes in geniculate unit activity of urethane-anaesthetized and freely moving rats were investigated during conditioning. The conditioned stimulus (CS) was a flash which was paired with an electrical stimulation of the tail as unconditioned stimulus (US). The discharge rates evoked by the CS during forward conditioning were significantly higher in responding units than those evoked by reversal of CS and US (backward conditioning) or by pseudoconditioning. Tail stimulation alone did not cause significant changes in the firing rate of most of the neurons. In 25% of the investigated neurons the facilitation of activity evoked by forward conditioning persisted during an extinction period of more than 15 min. The effect of conditioning on neuronal activity appeared to be comparable in urethane-anaesthetized rats and in freely moving ones which responded to the US with a slight freezing behavior.

Anesthesia↗
PubMed1989

In vitro formation of organ-specific ultimate carcinogens of 4-dimethylaminoazobenzene and urethan by microsomes.

In order to determine the organ-specific carcinogenicity of 4-dimethylaminoazobenzene (4-DAB) and urethan, their metabolites formed in vitro by incubation with the microsomes from liver, lungs, brain and kidneys of rats were isolated by thin-layer chromatography. 4-DAB was found to be metabolized to give two major products, 4-aminoazobenzene and N-hydroxy-4-aminoazobenzene, only when incubated with liver microsomes. These metabolites were not detected when microsomal suspensions of lungs, brain and kidneys were used. Similarly, urethan was found to yield three metabolites, N-hydroxy derivative of ethyl carbamate, N-hydroxyvinyl carbamate, and epoxy derivative of ethyl carbamate, on incubation with lung microsomes, but not with the microsomes from liver, brain and kidneys. As the potential carcinogenic moieties were only formed by incubating these two compounds with the microsomes of their target organs, their organ-specific carcinogenicity may be explained.

Animals↗
PubMed1996

Influence of urethane anesthesia on neural processing in the auditory cortex analogue of a songbird.

Functional maps of auditory response areas were derived from multi-unit recordings in the caudal telencephalon of the starling (Sturnus vulgaris L.). A regular grid of recording sites with distances of 200 microns horizontally and 100 microns vertically was placed over the auditory cortex analogue. Within one plane, mapping of auditory responses was first performed in the awake bird and then repeated under urethane anesthesia. The data from both experimental approaches differ considerably. Urethane reduces the spontaneous discharge rate significantly. Under anesthesia, inhibition decreases in all auditory subunits. Excitation is less affected. Eight auditory subcenters were divided into three groups according to the changes in their excitatory responses. In the first group 'on' and sustained excitation changed only weakly. These areas are thought to receive direct inputs from the diencephalon. In the second group, 'on' and sustained excitation are substantially reduced. These subcenters seem to receive projections from other forebrain areas. In subunits of the third group, an increase in sustained excitation is correlated to a decrease in inhibition. Within some specific centers, distinct natural calls, for example the bird's own song, elicit stronger responses under anesthesia than other stimuli.

Acoustic Stimulation↗
PubMed2005

Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).

A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).

Amides↗
PubMed2005

Supraspinal and spinal alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid and N-methyl-D-aspartate glutamatergic control of the micturition reflex in the urethane-anesthetized rat.

Effects of i.c.v. and i.t. administration of (3SR,4aRS,6RS,8aRS)-6-[2-(1H-tetrazol-5-yl)ethyl]decahydroisoquinoline-3-carboxylic acid (LY215490), a competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist and MK-801, a non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist on the micturition reflex were evaluated in urethane-anesthetized rats, to determine if glutamatergic mechanisms in brain as well as spinal cord are important for the control of micturition. I.c.v. or i.t. injection of LY215490 in low doses (0.01-0.03 microg) did not change rhythmic bladder or external urethral sphincter (EUS) electromyogram (EMG) activity during continuous cystometrograms (CMGs; 0.21 ml/min), whereas higher doses (0.1-1 microg) markedly suppressed these responses. During single CMGs (0.04 ml/min), 0.1-1 microg i.c.v. or 0.1-10 microg i.t. doses increased volume threshold and pressure threshold for inducing micturition, and decreased bladder contraction amplitude and voiding efficiency. MK-801 in low doses (0.6 microg i.c.v. or 0.6-1.8 microg for i.t.) did not change bladder contraction amplitude or EUS EMG activity during continuous CMGs, whereas higher doses 6-60 microg markedly suppressed these responses. During single CMGs, MK-801 (6-60 microg i.c.v. or 60 microg i.t.) increased volume threshold and pressure threshold, and decreased voiding efficiency and bladder contraction amplitude. Pretreatment i.c.v. with MK-801 in a dose 1.8 microg which alone had little effect on bladder contraction amplitude and EUS EMG activity, markedly enhanced depressant effects of LY215490 (0.03 microg i.c.v.) on these responses. Administration of same doses of drugs by i.t. route did not elicit a similar synergistic interaction. These data indicate that in urethane-anesthetized rats glutamatergic mechanisms in brain and spinal cord are essential for controlling micturition and that interactions between AMPA and NMDA glutamatergic transmission are important at supraspinal but not spinal sites.

Anesthesia↗