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PubMed2003

A method to study preovulatory surges of gonadotropins.

The aim of this study was to describe and validate a method to evaluate the preovulatory surges of gonadotropins in rats submitted to anesthesia and implantation of a jugular vein cannula in the morning of proestrus and to withdrawal of serial blood samples in the afternoon of the same day. In experiment I, to choose an adequate anesthetic, cycling female rats were anesthetized in the morning of proestrus (10:00-11:00 h) with tribromoethanol, ketamine/xylazine or tiletamine/zolazepam and a Silastic cannula was implanted into the jugular vein. Blood samples (0.6 ml) were withdrawn hourly between 12:00 and 18:00 h of the same day and, on estrus morning, the rats were decapitated and the number of ova was counted. The preovulatory gonadotropin surges as well as ovulation occurred in rats anesthetized with tribromoethanol, while they were prevented by ketamine/xylazine or tiletamine/zolazepam. To investigate if the jugular cannulation under tribromoethanol anesthesia and serial blood sampling performed in experiment I altered the magnitude of the gonadotropin surges and the number of ova, intact rats (control) or rats anesthetized with tribromoethanol followed or not by jugular vein cannulation were decapitated at 16:00 h of proestrus and in the morning of estrus. The magnitude of preovulatory gonadotropin surges and the number of ova were not different among groups. Thus, since neither tribromoethanol nor surgical procedures or serial blood sampling altered the preovulatory gonadotropin surges or the ovulation process, this method seems to be suitable for this sort of study in rats.

Anesthesia↗
PubMed1999

Peritonitis in Nude Mice in a Xenograft Study.

After 30 Sim: (NCR) nu/nu mice were anesthetized with intraperitoneal tribromoethanol, they were injected with 106 human breast cancer cells or phosphate buffered saline (PBS) into the mammary fat pad through a surgical incision. Over the next six days, 24 of 30 mice became ill or died. Necropsies showed peritonitis, and a variety of bacteria were isolated from the peritoneal cavities of the mice. The tribromoethanol solution, PBS solution, and neoplastic cell line were all cultured and were microbiologically negative. Three immunocompetent mice were subsequently injected intraperitoneally with the same tribromoethanol solution used for the 30 nude mice. All three of the immunocompetent mice showed histologic evidence of peritonitis, but only one yielded positive peritoneal bacterial cultures and showed gross evidence of peritonitis. The tribromoethanol solution, previously reported to cause peritonitis, likely induced a chemical peritonitis in these mice, and the bacteria isolated were a secondary infection from normal gastrointestinal flora. We conclude that adequate mixing and storage of tribromoethanol are essential and that it is a safe and effective anesthetic when properly used.

Journal Article↗
PubMed1975

Potentiation by urethane and inhibition by pentobarbitone of oxytocin release in vitro.

Isolated rat neural lobes were incubated in vitro in Locke's solution containing anaesthetic quantities of urethane, pentobarbitone or tribromoethanol. The oxytocin content of the incubation medium was estimated before, during and after stimulation of the tissue by raising the potassium chloride concentration from 5-6 to 56 mmol/l. Urethane (25 mmol/l) significantly potentiated oxytocin release (P less than 0-01) whereas tribromoethanol (0-5 mmol/l) had no obvious effect and pentobarbitone (0-4 mmol/l) significantly (P less than 0-01) inhibited its release. Reduction of the sodium chloride concentration in the medium potentiated the release of oxytocin in each case but did not alter its pattern. Urethane which increased secretion of oxytocin also increased calcium ion uptake by the neural lobes and pentobarbitone which decreased oxytocin release decreased calcium ion uptake. The results may explain why the blood concentration of the neurohypophysial hormones tends to be higher in rats anaesthetized with urethane than with tribromoethanol. Inhibition of hormone release by pentobarbitone suggests that this anaesthetic is unsuitable for use in studies of neurohypophysial hormone release. A partial explanation of the anaesthetic properties of urethane and pentobarbitone may also have been found if the release of neurotransmitter substances is influenced in a similar manner.

Animals↗
PubMed2002

Involvement of NMDA receptors in the pressor response to microinjection of 5-HT3 agonist into the NTS of awake rats.

Previous studies have shown that the activation of 5-HT3 receptors in the nucleus tractus solitarii (NTS) increases the baseline mean arterial pressure (MAP). In the present study, we evaluated the possible involvement of NMDA receptors in this pressor response. Four days before the experiments, under tribromoethanol anesthesia, rats received two guide cannulas in the direction of the NTS, and 1 day before the experiments, under tribromoethanol anesthesia, the femoral artery was cannulated for pulsatile arterial pressure (PAP), MAP, and heart rate (HR) measurements. On the day of the experiments, 2-methyl-serotonin, a 5-HT3 agonist, was microinjected into the NTS after microinjection of saline or AP-5, a selective NMDA receptor antagonist. Microinjection of 2-methyl-serotonin (5 nmol/50 nl) into the NTS after the vehicle (saline) produced a significant increase in MAP (+ 20 +/- 5 mm Hg, n = 8) while microinjection of 2-methyl-serotonin after microinjection of AP-5 (10 nmol/50 nl) produced no change in baseline MAP (-1 +/- 3 mm Hg, n = 11). Microinjection of AP-5 into the NTS produced no significant changes in the baseline MAP and HR. The data show that the increase in MAP in response to microinjection of a 5-HT3 agonist into the NTS is dependent on NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed2004

Influence of O(3)/O(2)-pneumoperitoneum as an oxidative stressor on duration of anaesthesia, loss of different reflexes and cytokine mRNA expression.

We analysed the effect of intraperitoneal insufflated ozonized oxygen on the anaesthetic strength generated by tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane in male Wistar rats. High dosages of anaesthetic drugs normally used for deep surgical anaesthesia were injected. The ozonized oxygen gas mixture was given five times daily on five consecutive days at 0.8 mg ozone/kg body weight before anaesthesia. The reflexes were measured 15, 30, 60, 90, 120, 180, and 240 min after injection of the anaesthetic drug. The sleeping time and the loss and regain of six different reflexes on noxious and non-aversive stimuli were recorded during the 4 h of observation. O(3)/O(2)-pneumoperitoneum (O(3)/O(2)-PP) reduced the sleeping time induced by tribromoethanol and ketamine/xylazine and increased it for chloral hydrate and pentobarbital. In accordance to the changes in the duration of anaesthesia, the O(3)/O(2)-PP induced significant changes in the loss of different reflexes. Additionally, the modulatory effect of the anaesthetic drugs on splenic cytokine mRNA expression was further influenced by O(3)/O(2)-PP. Thus, the influence of an oxidative stressor on anaesthetic potency and on the resting immune system has to be taken into account for experimental designs in which surgical anaesthesia is necessary for small laboratory animals.

Analysis of Variance↗
PubMed2004

Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen.

We examined the effect of five anaesthetic drugs commonly used in laboratory animal research (tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane) on the expression of four pro-inflammatory cytokines. The anaesthetic agents were applied at dosages normally used for deep surgical anaesthesia. Semiquantitative image analysis of interleukin (IL)-1beta, IL-2, IL-6, and tumour necrosis factor alpha (TNFalpha) mRNA expression in the spleen of male Wistar rats 4 h after application of the anaesthetic drugs showed that these had moderate immunomodulatory effects. Ketamine/xylazine, chloral hydrate, and pentobarbital enhanced the basal expression of IL-1beta and IL-6 mRNA in rat spleen, while urethane reduced splenic IL-1beta mRNA expression. Tribromoethanol, ketamine/xylazine, and urethane reduced the basal TNFalpha mRNA levels, whereas TNFalpha mRNA expression was unaffected by chloral hydrate and by pentobarbital. The data demonstrate that these anaesthetics have slight, but significant, effects on the basal immune status of rats.

Adjuvants, Immunologic↗
PubMed1998

Growth Hormone (GH) but not IGF-I-Secretion is Stimulated in Aged Rats by Chronic Hexarelin and GHRP-6 administration.

The present studies were designed to investigate in aged rats (22-24 months old) the effectiveness and specificity of acute hexarelin (HEXA) administration on the release of growth hormone (GH), the minimal dose of the peptide that produces the maximal GH secretion and the effects of long term treatment with HEXA or growth hormone releasing peptide (GHRP-6) on plasma levels of GH and IGF-1. To select the appropriate anesthetic to obtain serial blood samples, the GH releasing activity of HEXA (30 µg/kg i.v.) was tested in young rats anesthetized with tribromoethanol and ketamine-xylazine, and the results were compared with those obtained from conscious freely moving rats. When compared to the changes found in conscious rats, the GH-response to HEXA was increased by ketamine-xylazine anesthesia, while it was decreased by tribromoethanol. Therefore, all subsequent experiments were performed in conscious freely moving rats. To determine the minimal effective dose of HEXA and GHRP-6 in aged animals, different doses (5, 10, 20, 40, and 80 µg/kg) of either HEXA or GHRP-6 were administered subcutaneously to young and aged rats. It was found that 20 µg/kg bw of HEXA or GHRP-6 was the minimal dose producing the maximal GH response. Plasma PRL and LH determinations in the animals injected with the minimal dose showed that HEXA and GHRP-6 stimulate the GH release specifically. Based on the results obtained in the latter experiments, young and aged rats were chronically treated with s.c. injections of 20 µg/kg twice a day for 15 or 30 days. At the end of the experiments, animals were acutely tested with s.c. injection of the same dose (20 µg/kg). It was found that both young and aged animals released GH in response to the repeated administration of GH releasing peptides after 15 days of treatment. However, after 30 days of treatment plasma GH did not change when young and aged HEXA treated animals were acutely tested with such peptide, but increased significantly in the GHRP-6 treated animals when they were acutely tested with GHRP-6. In response to the long term treatment with the GH-releasing peptides, plasma IGF-I levels increased in young animals when they were acutely tested with the corresponding peptide. However, plasma IGF-I levels in aged rats were not modified by the acute administration of either HEXA or GHRP-6 after 15 or 30 days of treatment. This study showed that: 1. HEXA and GHRP-6 stimulated GH release in aged rats and the magnitude of GH responses was similar to that in young rats; 2. the minimal dose of HEXA and GHRP-6 resulting in maximal GH response was 20 g/kg and such dose of HEXA specifically stimulated GH secretion in aged rats; 3. fifteen but not 30 days treatment of aged rats with such small dose of HEXA resulted in a similar GH response to subsequent stimulation with the same peptide; 4. plasma IGF-I responses to an acute administration of HEXA or GHRP-6 in rats chronically treated with the same peptide vanished with aging.

Journal Article↗
PubMed2000

Effect of anesthetics on reflex micturition in the chronic cannula-implanted rat.

It is well known that urethane is a suitable anesthetic for acute studies and has been extensively recommended for investigations related to micturition physiology. This is mainly because of the capability of urethane anesthesia to spare reflex micturition as well as its easily established long-lasting and stable anesthetic level. However, urethane anesthesia is usually restricted to acute experiments due to its potential toxicity. This study searched for an alternative to urethane that would be suitable for studies in which recovery from anesthesia was needed. The list of administered drugs was as follows: pentobarbital, thiobutabarbital, ketamine-acepromazine, ketamine-diazepam, tiletamine-zolazepam, fentanyl-droperidol, alphaxalone-alphadolone, propofol, isoflurane, methoxyflurane, azaperone, tribromoethanol, and buprenorphine. Among these drugs, only tiletamine-zolazepam spared the reflex micturition contractions. However, the duration of this anesthesia was too short (approximately 30 minutes) to complete the necessary testing and additional dosing of the anesthetic generally obliterated the micturition reflex. On the other hand, rats given i.v. urethane infusion (10% solution in 0.9% saline, 3.2-4.0 mg/kg/min, total dose 0.56-1.03 g/kg) maintained a stable anesthesia that permitted both reflex micturition and stereotaxic procedures. Rats moved spontaneously 3-16 hours after cessation of i.v. urethane anesthesia and completely recovered in 2 days without significant after-effects. Bladder function was normal. No pathological changes were seen 1 week later. The present results suggest that urethane is the most suitable anesthetic for acute and chronic physiological experiments that require demonstration of reflex micturition. Neurourol. Urodynam. 19:87-99, 2000.

Anesthesia↗
PubMed1989

Lysosomal mutations increase susceptibility to anaesthetics.

The anaesthetic responses of homozygous mutant mice were compared with those of their normal heterozygous littermates. The two recessive mutations studied were beige (bg) and reduced pigmentation (rp). Homozygosity for either significantly increased the sleeping time of both sexes after treatment with pentobarbital, tribromoethanol or the steroid anaesthetic alphaxalone.

Anesthesia↗
PubMed2005

Involvement of NMDA receptors in the hypotensive response to the injection of L-glutamate into the lateral hypothalamus of unanesthetized rats.

We report that microinjections of L-glutamate (L-glu) or N-methyl-D-aspartic acid (NMDA) in the lateral hypothalamus (LH) of unanesthetized rats caused a hypotensive response. Guide cannulas were stereotaxically placed in the LH 3 days before the experiments, under tribromoethanol anesthesia. One day before the experiments, the femoral artery was cannulated for pulsatile arterial pressure (PAP), mean arterial pressure (MAP) and heart rate (HR) measurements. In the first experiment, unanesthetized rats received microinjections of 2.5, 5.0 or 10.0 nmol/100 nL of L-glu in the LH. Dose-dependent hypotensive responses were observed, without significant concomitant changes in heart rate. In a second group of experiments, 5.0 nmol of L-glu was microinjected into the LH before and 10 min after pretreatment with glutamatergic antagonists. Pretreatments with the non-selective ionotropic glutamatergic-receptor antagonist kynurenic acid or the selective NMDA receptor antagonists AP-7 and LY235959 significantly reduced the hypotensive response to microinjection of L-glu in the LH. Pretreatment with the selective AMPA-receptor antagonist NBQX or with vehicle did not affect the hypotensive response. The present results suggest that the hypotensive response to the injection of L-glu into the LH is mediated by NMDA receptors.

Analysis of Variance↗
PubMed2005

Respiratory and autonomic responses to microinjection of NMDA and AMPA into the commissural subnucleus of the NTS of awake rats.

The changes in mean arterial pressure (MAP) and respiratory frequency (RF) in response to microinjection of NMDA or AMPA into the commissural subnucleus of the NTS (comNTS) at the calamus scriptorius level of awake rats were evaluated. Under tribromoethanol anesthesia, the rats received guide-cannulae in direction of the NTS and a catheter was inserted into the femoral artery for measurement of arterial pressure. Changes in RF were evaluated with the rats inside a plethysmographic chamber. Randomly microinjections of 5 doses of NMDA (0.001, 0.01, 0.1, 1.0 and 2 nmol/50 nL; n = 10) or AMPA (1, 5, 10, 25 and 50 pmol/50 nL; n = 8) into the comNTS were performed at 15 min intervals and produced a dose-dependent increase in MAP [NMDA (3 +/- 2, 4 +/- 3, 25 +/- 4, 41 +/- 4 and 51 +/- 4 mm Hg) and AMPA (0 +/- 1, 14 +/- 4, 17 +/- 3, 27 +/- 5 and 34 +/- 3 mm Hg)]. Microinjection of NMDA (1 nmol/50 nL; n = 7) or AMPA (50 pmol/50 nL; n = 4) into the comNTS produced a long lasting apnea. The pressor responses to microinjection of NMDA or AMPA into the comNTS were blocked by prazosin, a alpha(1)-adrenoceptor antagonist, indicating that the increase in arterial pressure in both cases was sympathetically mediated. The data show that microinjection of NMDA and AMPA into the comNTS produced pressor response and apnea, indicating that both ionotropic l-glutamate receptors may play a role in the neurotransmission/neuromodulation of the autonomic and respiratory components of the cardiovascular reflexes at this level.

Analysis of Variance↗
PubMed2004

Intracerebroventricular tryptophan increases heating and heat storage rate in exercising rats.

The role of increased hypothalamic tryptophan (TRP) availability on thermoregulation and rates of core temperature increase and heat storage (HS) during exercise was studied in normal untrained rats running until fatigue. The rats were each anesthetized with 2.5% tribromoethanol (1.0 ml kg(-1) ip) and fitted with a chronic guiding cannula attached to the right lateral cerebral ventricle 1 week prior to the experiments. Immediately before exercise, they were randomly injected through these cannulae with 2.0 microl of 0.15 M NaCl (SAL; n=6) or 20.3 microM L-TRP solution (n=7). Exercise consisted of running on a treadmill at 18 m min(-1) and 5% inclination until fatigue. Body temperature was recorded before and during exercise with a thermistor probe implanted into the peritoneal area. Rates of core temperature increase (HR, degrees C min(-1)) and heat storage (HSR, cal min(-1)) were calculated. TRP-treated rats showed a rapid increase in body temperature which was faster than that observed in the saline-treated group during the exercise period. The TRP group also showed a higher rate of core temperature increase and HS. TRP-treated rats that presented higher HR and HSR also fatigued much earlier than saline-treated animals (16.8+/-1.1 min TRP vs. 40+/-3 min SAL). This suggests that the reduced running performance observed in TRP-treated rats is related to increased HR and HSR induced by intracerebroventricular injection of TRP in these animals.

Animals↗
PubMed2005

Interaction between arginine vasopressin and angiotensin II receptors in the central regulation of sodium balance.

We speculated that the influence of lateral preoptic area (LPO) in sodium balance, involves arginine8-vasopressin (AVP) and angiotensin (ANG II) on Na+ uptake in LPO. Therefore, the present study investigated the effects of central administration of specific AVP and ANG II antagonists (d(CH2)5-Tyr (Me)-AVP (AAVP) and [Adamanteanacetyl1, 0-ET-d-Tyr2, Val4, Aminobutyryl6, Arg(8,9)]-AVP (ATAVP) antagonists of V1 and V2 receptors of AVP. Also the effects of losartan and CGP42112A (selective ligands of the AT1 and AT2 angiotensin receptors, respectively), was investigated on Na+ uptake and renal fluid and electrolyte excretion. After an acclimatization period of 7 days, the animals were maintained under tribromoethanol (200 mg/kg body weight, intraperitonial) anesthesia and placed in a Kopf stereotaxic instrument. Stainless guide cannula was implanted into the LPO. AAVP and ATAVP injected into the LPO prior to AVP produced a reduction in the NaCl intake. Both the AT1 and AT2 ligands administered into the LPO elicited a decrease in the NaCl intake induced by AVP injected into the LPO. AVP injection into the LPO increased sodium renal excretion, but this was reduced by prior AAVP administration. The ATAVP produced a decreased in the natriuretic effect of AVP. The losartan injected into LPO previous to AVP decreased the sodium excretion and the CGP 421122A also decreased the natriuretic effect of AVP. The AVP produced an antidiuresis effect that was inhibited by prior administration into LPO of the ATAVP. The AAVP produced no change in the antidiuretic effect of AVP. These results suggest that LPO are implicated in sodium balance that is mediated by V1, V2, AT1 and AT2 receptors.

Angiotensin II↗
PubMed2002

Inhibition of pilocarpine-induced salivation in rats by central noradrenaline.

Peripheral treatment with cholinergic or adrenergic agonists results in salivation and the possibility of synergy between cholinergic and adrenergic efferent mechanisms in the control of salivation has been proposed. Central injections of the cholinergic agonist pilocarpine also induce salivation, while the effects of central injections of noradrenaline (norepinephrine) are not known. Here (a) the effects of intracerebroventricular (i.c.v.) injection of noradrenaline on the salivation induced by i.c.v. or intraperitoneal (i.p.) injection of pilocarpine and (b) the receptors involved in the effects of central noradrenaline on pilocarpine-induced salivation were investigated. Male Holtzman rats with a stainless-steel guide cannula implanted into the lateral ventricle were used. Rats were anaesthetized with tribromoethanol (200mg/kg body weight) and saliva was collected on small, preweighed cotton balls inserted into the animal's mouth. Noradrenaline (40, 80 and 160 nmol/1 microl) injected i.c.v. reduced the salivary secretion induced by pilocarpine (0.5 micro mol/1 microl) injected i.c.v.. Noradrenaline (80 and 160 nmol/1 microl) injected i.c.v. also reduced the salivation induced by pilocarpine (4 micromol/kg) injected i.p. Previous treatment with the alpha(2)-adrenergic receptor antagonists RX 821002 (40, 80 and 160 nmol/1 microl) or yohimbine (160 and 320 nmol/1 microl) abolished the inhibitory effect produced by i.c.v. injection of noradrenaline on pilocarpine-induced salivation in rats. Prazosin (alpha(1)-adrenergic receptor antagonist) injected icv did not change the effect of noradrenaline on pilocarpine-induced salivation. Prior icv injection of only RX 821002 (80 or 160 nmol/1 microl) or yohimbine (320 nmol/1 microl) increased pilocarpine-induced salivation. The results show that (1) contrary to its peripheral effects, noradrenaline acting centrally inhibits cholinergic-induced salivation in rats; (2) central mechanisms involving alpha(2)-adrenergic receptors inhibit pilocarpine-induced salivation.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed1998

5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated vagus nerve: modulation by trichloroethanol and related alcohols.

The ability of 2,2,2-trichloroethanol (TCE) and related alcohols to modify the 5-hydroxytryptamine3 (5-HT3) receptor-mediated depolarisation of the rat isolated cervical vagus nerve were investigated by extracellular electrophysiological recording using the 'grease gap' technique. TCE at millimolar concentrations increased the magnitude of the 5-HT3 receptor-mediated depolarisations of the rat vagus nerve by a number of agonists (5-HT, phenylbiguanide (PBG), quipazine). Concentration response curves generated for the 5-HT3 receptor agonists. 5-HT and PBG, in the absence and presence of TCE (5 mM) indicated that the potentiation in agonist-induced depolarisation was due to an increase in both agonist potency and apparent efficacy. Following apparent complete 5-HT3 receptor desensitisation (induced by either 5-HT or PBG; 100 microM for 90 min), application of TCE (5 mM) in the continued presence of either agonist induced a depolarisation of the vagus nerve. In addition to TCE, a number of related alcohols (tribromoethanol, isopentanol and 5-chloropentanol but not ethanol) at millimolar concentrations also potentiated depolarisation of the vagus nerve induced by 5-HT. Combined application of both TCE (0.1-20 mM) and isopentanol (20 mM) indicated that the potentiation of the 5-HT3 receptor-mediated depolarisation by these alcohols was not additive. The present studies indicate that the 5-HT3 receptor expressed on the cervical vagus nerve is susceptible to allosteric modulation by a number of alcohols including the anaesthetic agent TCE. Such an interaction may have relevance to the nausea and vomiting experienced by some patients following recovery from general anaesthesia.

Animals↗
PubMed1999

Sympathetic mediation of salivation induced by intracerebroventricular pilocarpine in rats.

Central cholinergic activation by pilocarpine induces salivation dependent on the integrity of forebrain areas. The present work investigates the autonomic mediation of this salivation. Pilocarpine (500 nmol/rat) was injected into the lateral ventricle (LV) of tribromoethanol-anesthetized adult male rats. Preweighed cotton balls were inserted into the oral cavity and weighed again 7 min later. Alpha-adrenoceptor antagonists (3-50 micromol/kg) prazosin (alpha1), yohimbine (alpha2) or propranolol (beta) injected intraperitoneally (i.p.) produced, 80%, 20% and 0% inhibition respectively of the LV pilocarpine-induced salivation. Intracerebroventricular injections (160 nmol) of the antagonists did not alter the effects of pilocarpine injected into the LV. Bilateral section of chorda tympani nerve or bilateral sympathetic cervical ganglionectomy produced 0% and 40% inhibition of pilocarpine-induced salivation, respectively. Ganglionectomy did not alter salivation induced by i.p. injection of pilocarpine (4 micromol/kg). The results indicate that there is a large sympathetic contribution to the salivation induced by central cholinergic activation.

Adrenergic Antagonists↗
PubMed2001

Moxonidine reduces pilocarpine-induced salivation in rats.

Cholinergic agonists activate salivation and the alpha2-adrenergic and imidazoline receptor agonists induce opposite effects. In the present study, we investigated the effects of intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of moxonidine (an alpha2-adrenergic and imidazoline receptor agonist) on the salivation induced by the cholinergic agonist pilocarpine. Male Holtzman rats with stainless steel cannula implanted into the lateral ventricle (LV) were used. In rats anesthetized with tribromoethanol (200 mg kg(-1), saliva was collected using pre-weighed small cotton balls inserted in the animal's mouth. The treatment with moxonidine (5, 10 and 20 nmol in 1 microl) injected i.c.v. reduced the salivation induced by pilocarpine (1 mg kg(-1)) injected i.p. (48 +/- 5, 17 +/- 2 and 15 +/- 2 mg min(-1) vs. control, 73 +/- 7 mg min(-1)). The same doses of moxonidine injected i.c.v. also reduced the salivary secretion induced by pilocarpine (500 nmol in 1 microl) injected i.c.v. (44 +/- 1, 14 +/- 2 and 20 +/- 3 mg min(-1) vs. control, 51 +/- 2 mg min(-1)). Injection of moxonidine (20 nmol in 0.1 ml) i.p. produced no change on i.p. pilocarpine-induced salivation (58 +/- 4 mg min(-1) vs. control, 50 +/- 4 mg min(-1)). The results show that central, but not peripheral, injection of moxonidine inhibits pilocarpine-induced salivation, suggesting that central mechanisms activated by alpha2-adrenergic/imidazoline agonists inhibit cholinergic-induced salivation in rats.

Animals↗
PubMed2000

The actions of ether, alcohol and alkane general anaesthetics on GABAA and glycine receptors and the effects of TM2 and TM3 mutations.

The actions of 13 general anaesthetics (diethyl ether, enflurane, isoflurane, methoxyflurane, sevoflurane, chloral hydrate, trifluoroethanol, tribromoethanol, tert-butanol, chloretone, brometone, trichloroethylene, and alpha-chloralose) were studied on agonist-activated Cl(-) currents at human GABA(A) alpha(2)beta(1), glycine alpha(1), and GABA(C) rho(1) receptors expressed in human embryonic kidney 293 cells. All 13 anaesthetics enhanced responses to submaximal (EC(20)) concentrations of agonist at GABA(A) and glycine receptors, except alpha-chloralose, which did not enhance responses at the glycine alpha(1) receptor. None of the anaesthetics studied potentiated GABA responses at the GABA(C) rho(1) receptor. Potentiation of submaximal agonist currents by the anaesthetics was studied at GABA(A) and glycine receptors harbouring mutations in putative transmembrane domains 2 and 3 within GABA(A) alpha(2), beta(1), or glycine alpha(1) receptor subunits: GABA(A) alpha(2)(S270I)beta(1), alpha(2)(A291W)beta(1), alpha(2)beta(1)(S265I), and alpha(2)beta(1)(M286W); glycine alpha(1)(S267I) and alpha(1)(A288W). For all anaesthetics studied except alpha-chloralose, at least one of the mutations above abolished drug potentiation of agonist responses at GABA(A) and glycine receptors. alpha-Chloralose produced efficacious direct activation of the GABA(A) alpha(2)beta(1) receptor (a 'GABA-mimetic' effect). The other 12 anaesthetics produced minimal or no direct activation of GABA(A) and glycine receptors. A non-anaesthetic isomer of alpha-chloralose, beta-chloralose, was inactive at GABA(A) and glycine receptors and did not antagonize the actions of alpha-chloralose at GABA(A) receptors. The implications of these findings for the molecular mechanisms of action of general anaesthetics at GABA(A) and glycine receptors are discussed.

Alcohols↗