Biomedical subjects

R M Quock

Publications and source records attributed to R M Quock.

At least 37 records · Page 2Linked to original sources

PubMed1994

Effect of opioid peptide antisera on nitrous oxide antinociception in rats.

This study was performed to examine the effects of ICV injection of antiserum against beta-endorphin (beta-EP) or methionine-enkephalin (ME) on nitrous oxide-induced antinociception in rats using the hot plate test. The injection of beta-EP antiserum reversed the antinociceptive effect of nitrous oxide in a dose-related manner up to 200 micrograms/rat. However, antagonism of nitrous oxide by 400 micrograms beta-EP antiserum was comparable to that produced by 200 micrograms. On the other hand, similar amounts of ME antiserum had little effect against nitrous oxide antinociception. These findings suggest that beta-EP may play an important role in the antinociceptive effect of nitrous oxide.

Analgesics↗

PubMed1994

Antagonism of nitrous oxide antinociception in the rat hot plate test by site-specific mu and epsilon opioid receptor blockade.

The analgesic property of the anesthetic gas N2O has long been known and used to treat pain in clinical medicine and dentistry. The present study was conducted to identify by subtype and possible location the brain opioid receptors that mediate N2O antinociception in rats. A 5-min exposure to 70% N2O consistently evoked an antinociceptive effect in the hot plate test. This drug effect was partly antagonized in dose-related fashion by i.c.v. pretreatment with naltrexone, D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 and beta-endorphin, which block multiple, mu and epsilon opioid receptors, respectively. However, the N2O-evoked antinociception was unaffected by i.c.v. pretreatment with either the delta opioid antagonist naltrindole or the kappa opioid antagonist nor-binaltorphimine. When D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 was administered intracerebrally directly into the periaqueductal gray, N2O antinociception was partly antagonized in a dose-dependent manner. The antinociceptive response to N2O was uninfluenced by beta-endorphin administered into the periaqueductal gray. The findings of these pharmacological antagonism studies are consistent with the hypothesis that exposure to N2O causes a neuronal release of beta-endorphin. These results indicate that supraspinal mu and epsilon opioid receptors mediate N2O antinociception in the rat hot plate paradigm and that one central site of such mu but not epsilon opioid receptors is the periaqueductal gray.

Amino Acid Sequence↗

PubMed1994

Inhibitors of nitric oxide synthesis antagonize nitrous oxide antinociception in mice and rats.

Administration of the anesthetic gas N2O evoked an antinociceptive effect in two rodent antinociception paradigms. In the mouse abdominal constriction test, pretreatment with the nitric oxide synthase (NOS) inhibitor L-NG-nitroarginine (L-NOARG) caused dose-related antagonism of the antinociceptive effect of N2O but not of either morphine or trans(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate. This antinociceptive effect was also antagonized by systemic pretreatment with the NOS inhibitors L-NG-nitroarginine methyl ester (L-NAME) and L-NG-monomethylnitroarginine. The antagonism of N2O by L-NOARG and L-NAME was completely reversed by i.c.v. administration of L-arginine but not D-arginine. In the absence of NOS inhibition, N2O antinociception was potentiated by i.c.v. treatment with L-arginine but not D-arginine. The i.c.v. pretreatment with L-NAME also reduced N2O antinociception; this antagonism was also stereospecifically reversed by L-arginine. In the rat hot plate test, the antinociceptive response to 70% N2O was antagonized in dose-related manner by i.c.v. pretreatment with L-NOARG or L-NAME. N2O antinociception was restored by i.c.v. treatment with L-arginine but not D-arginine. However, neither L-arginine nor D-arginine alone affected N2O antinociception. These results implicate a key role for NO in the mediation of the antinociceptive effects of N2O in both mice and rats.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Strain-dependent differences in responsiveness of mice to nitrous oxide (N2O) antinociception.

N2O antinociception was assessed in eight inbred and two outbred mouse strains. Results indicated the following order of responsiveness among the 10 strains: A/J (most sensitive), C57BL/6ByJ, C57BL/6J, BALB/cByJ, C3H/HeJ, Swiss-Webster, CXBK/ByJ, ICR, CBA/J and DBA/2J (least sensitive). These results demonstrate significant strain-dependent differences in antinociceptive responsiveness to N2O. The weak antinociceptive response to N2O in the DBA/2J strain, which is sensitive to morphine and U-50, 488H, indicates some underlying neurobiological difference in the DBA/2J mouse that imparts resistance to N2O. The responsiveness of CXBK/ByJ mice to N2O indicates that mu-opioid receptors may not play an important role in N2O antinociception in mice.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1993

Nitrous oxide induces an anxiolytic-like effect in the conditioned defensive burying paradigm, which can be reversed with a benzodiazepine receptor blocker.

To investigate the anxiolytic effects of nitrous oxide (N2O), male hooded rats were tested in the conditioned defensive burying (CDB) test, a paradigm that exploits a propensity of rats to bury objects associated with aversive stimulation. A single, brief electrical shock was delivered to rats upon contact with an electrified prod, before exposure to one of four mixtures of N2O and oxygen (O2) (10-40% N2O) or room air (RA). Compared to RA-exposed animals, rats exposed to N2O exhibited a concentration-related reduction in duration and height of prod-directed "defensive" burying with floor bedding material; these measures reached statistical significance at 30% N2O. Pretreatment with 20 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, effectively antagonized a 30% N2O-induced decrease in burying. Horizontal locomotion and rearing were not significantly affected at concentrations of N2O that attenuated prod-directed burying. Treatment with the benzodiazepine anxiolytic standard, chlordiazepoxide (2.5-10.0 mg/kg) also resulted in dose-related attenuation of burying behavior. These findings show that N2O can induce effects similar to those of known anxiolytics in this paradigm and suggest a benzodiazepine mechanism in its mediation.

Animals↗

PubMed1993

Benzodiazepine receptor-mediated behavioral effects of nitrous oxide in the rat social interaction test.

The present study was conducted to ascertain whether an anxiolytic effect of nitrous oxide was demonstrable in rats using the social interaction test and whether this drug effect might be mediated by benzodiazepine receptors. Compared to behavior of vehicle-pretreated, room air-exposed rats, rat pairs exposed to nitrous oxide showed a generally inverted U-shaped dose-response curve with the maximum increase in social interaction encounters occurring at 25% and significant increase in time of active social interaction at 15-35%; higher concentrations produced a sedative effect that reduced social interaction. Treatment with 5.0 mg/kg of the anxiolytic benzodiazepine chlordiazepoxide also increased social interaction. Pretreatment with 10 mg/kg of the benzodiazepine receptor blocker flumazenil, which alone had no effect, significantly antagonized the social interaction-increasing effects of both nitrous oxide and chlordiazepoxide. In summary, these findings suggest that nitrous oxide produces a flumazenil-sensitive effect comparable to that of chlordiazepoxide and implicate central benzodiazepine mechanisms in mediation of the anxiolytic effect of nitrous oxide.

Animals↗

PubMed1993

Dose-dependent antagonism and potentiation of nitrous oxide antinociception by naloxone in mice.

Administration of the anesthetic gas nitrous oxide (N2O) evoked a concentration-dependent antinociceptive effect in mice as assessed by the abdominal constriction test. Depending on the dose and route of pretreatment with the opioid receptor blocker naloxone, the N2O drug effect was either antagonized or potentiated. After s.c. pretreatment with milligram per kilogram doses of naloxone, dose-related antagonism occurred; picogram per kilogram doses potentiated N2O-induced antinociception. The i.c.v. pretreatment with microgram quantities of naloxone also antagonized N2O antinociception in a dose-related fashion; i.c.v. pretreatment with femtogram doses was without effect. On the other hand, intrathecal (i.t.) pretreatment with femtogram quantities of naloxone potentiated N2O antinociception; i.t. pretreatment with microgram quantities continued to antagonize the antinociceptive effect. The same pattern of interaction was observed in mice challenged with the kappa opioid analgesic drug trans (+- 3,4-dichlow-N-methyl-N-[2-(1-pyrrolidinyl)cyclohexyl] benzeneacetamide methane sulfonate (U-50, 488H) after s.c., i.c.v. or i.t. pretreatments with high and low doses of naloxone. These results 1) demonstrate further similarities in the opioid receptor mediation of N2O and U-50, 488H antinociceptive effects and also 2) support the concept of high-affinity spinal opioid receptors, whose blockade by s.c.- or i.t.- but not i.c.v.-administered low-dose naloxone can potentiate the antinociceptive effects of both N2O and U-50,488H. These findings suggest that the antinociceptive effect of N2O might be modulated by a descending opioid system that inhibits analgesia.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1992

Benzodiazepine receptor mediation of behavioral effects of nitrous oxide in mice.

Nitrous oxide produces behavioral effects, the underlying mechanism of which is not known. In the mouse staircase test, exposure to nitrous oxide caused a reduction in rearing activity, an effect similar to that produced by benzodiazepines in this paradigm, when its opioid action on locomotion is blocked by naloxone. In this study, we tested whether effects of nitrous oxide might be mediated by benzodiazepine receptors, using chlordiazepoxide as a control. The abilities of nitrous oxide and chlordiazepoxide to reduce rearing were significantly attenuated in mice pretreated with the benzodiazepine receptor blocker flumazenil or rendered tolerant to benzodiazepines. These findings suggest an involvement of benzodiazepine receptors in mediation of certain behavioral effects of nitrous oxide.

Animals↗

PubMed1992

Possible involvement of nitric oxide in chlordiazepoxide-induced anxiolysis in mice.

Mice challenged with the anxiolytic benzodiazepine chlordiazepoxide exhibited significant increases in the percent of total entries into and percent of total time spent on open arms of an elevated plus maze. Systemic pretreatment with the nitric oxide synthase-inhibitor L-NG-nitro arginine (L-NOARG) antagonized these effects of chlordiazepoxide. This inhibitory effect of L-NOARG was stereospecifically and completely reversed by intracerebroventricular administration of L-arginine but not D-arginine. These findings suggest a possible role of nitric oxide in the anxiolytic effect of chlordiazepoxide in the elevated plus maze.

Amino Acid Oxidoreductases↗

PubMed1992

Naltrexone-sensitive analgesia following exposure of mice to 2450-MHz radiofrequency radiation.

To determine whether exposure to radiofrequency radiation (RFR) would induce sufficient thermal stress to activate endogenous opioid mechanisms, male Swiss Webster mice were exposed to 10, 15, and 20 mW/cm2 RFR in a 2450-MHz waveguide system for 10 min at specific absorption rates (SARs) of 23.7, 34.6, and 45.5 W/kg, respectively, then tested in the abdominal constriction paradigm. Confinement in the RFR exposure chamber alone did not appreciably alter body temperature but did appear to induce a stress-associated analgesia that was not blocked by naltrexone. Exposure of confined mice to RFR raised body temperature and further increased analgesia in an SAR-dependent manner. The high SAR-induced analgesia, but not the hyperthermia, was blocked by naltrexone. These findings suggest that 1) RFR produces SAR-dependent hyperthermia and analgesia, and 2) RFR-induced analgesia is mediated by opioid mechanisms while confinement-induced analgesia involves nonopioid mechanisms.

Analgesia↗

PubMed1992

Contrasting influences of 5-hydroxytryptamine receptors in nitrous oxide antinociception in mice.

5-Hydroxytryptamine (5-HT) mechanisms may play a role in opioid-mediated antinociception. Since opioid mechanisms have been implicated in nitrous oxide antinociception, this study was conducted to determine the possible role of 5-HT receptors in nitrous oxide antinociception. Male Swiss Webster mice were pretreated with one of two 5-HT receptor blockers and then tested in the acetic acid abdominal constriction test for their antinociceptive response to nitrous oxide, the kappa-opioid agonist U-50,488H, or the mu-opioid agonist sufentanil. Results indicate that the 5-HT3 receptor blocker ICS-205,930 antagonized both nitrous oxide and U-50,488H effects but not that of sufentanil. Mianserin, a 5-HT1c/5-HT2 receptor blocker, effects but not that of sufentanil. Mianserin, a 5-HT1c/5-HT2 receptor blocker, potentiated effects of both nitrous oxide and U-50,488H but not that of sufentanil. These findings show similarities in nitrous oxide and U-50,488H antinociception and further support our hypothesis that nitrous oxide works through central kappa-opioid mechanisms in mice. The results also suggest different roles for 5-HT receptor subtypes in mediating or modulating the antinociceptive effect of nitrous oxide.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1991

Protection by U-50,488H against beta-chlornaltrexamine antagonism of nitrous oxide antinociception in mice.

Nitrous oxide antinociception in the abdominal constriction test was significantly reduced in mice pretreated intracerebroventricularly (i.c.v.) with beta-chlornaltrexamine (beta-CNA). However, this antagonism was reversed when the beta-CNA was co-administered i.c.v. with the kappa-opioid ligand U-50,488H but not the mu-opioid ligand CTOP. These findings further demonstrate that nitrous oxide antinociception in the mouse abdominal constriction paradigm is mediated by kappa- but not mu-opioid receptors.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1991

Increased apomorphine-induced hypothermia precedes development of hypertension in SHRs.

Apomorphine produced a greater hypothermic response in spontaneously hypertensive rats (SHRs) than in normotensive Wistar-Kyoto rats (WKYs). Experiments were conducted in SHRs and WKYs of three age groups to determine whether the increased hypothermic responsiveness to apomorphine occurs prior to the development of hypertension. The mean systolic blood pressures (SBPs) of SHRs and WKYs were comparable at 4-6 weeks of age. The mean SBP of SHRs were significantly greater than that of WKYs at both 8-10 and 12-15 weeks of age. Yet SHRs responded to apomorphine with significantly greater hypothermia than WKYs at all three ages. These findings indicate that the hyperresponsiveness of SHRs to apomorphine-induced hypothermia precedes the development of hypertension. This sequence of events is consistent with the hypothesis that central DA systems play a role in development of hypertension in SHRs.

Aging↗

PubMed1990

Mediation of nitrous oxide analgesia in mice by spinal and supraspinal kappa-opioid receptors.

Exposure to nitrous oxide produced concentration-dependent analgesia in the mouse abdominal constriction test. Intracerebroventricular or intrathecal pretreatment with naltrexone or nor-binaltorphimine significantly reduced nitrous oxide analgesia. However, similar pretreatment with beta-funaltrexamine had no appreciable effect. These findings suggest that nitrous oxide analgesia involves spinal and supraspinal kappa-opioid receptors.

Analgesics↗

PubMed1990

Effects of benzodiazepine agonist, inverse agonist and antagonist drugs in the mouse staircase test.

This study examined the effects of the benzodiazepine agonist midazolam and inverse agonist noreleagnine independently and in conjunction with the antagonist flumazenil in the mouse staircase test. According to this paradigm, the numbers of steps ascended (NSA) and rears (NR) reflect locomotor activity and anxiety, respectively. Midazolam reduced NR at doses that did not affect NSA; this NR-lowering effect was blocked by flumazenil. Noreleagnine increased NR at doses that did not affect NSA; this NR-elevating effect was also blocked by flumazenil. Effective antagonist doses of flumazenil alone had no effect on NR or NSA. The exactly opposite effects of midazolam and noreleagnine on NR and their antagonism by flumazenil are consistent with the postulated activities of these drugs at benzodiazepine receptors.

Animals↗

PubMed1990

Influence of chronic ethanol exposure on nitrous oxide analgesia in mice.

The purpose of this study was to determine whether sensitivity to nitrous oxide analgesia was altered by chronic ethanol exposure. Control mice exposed to 25%, 50%, and 75% nitrous oxide in oxygen demonstrated a concentration-related analgesic effect, as measured by the acetic acid abdominal constriction test. Other mice previously exposed to ethanol vapors for 72 h exhibited a significantly reduced sensitivity to nitrous oxide analgesia. The dose-response curve of the chronic ethanol-exposed group was shifted to the right of that of the control mice. These findings suggest the possibility that subjects with a history of alcohol abuse might have reduced responsiveness to nitrous oxide in a clinical setting.

Alcoholism↗

PubMed1990

A study of central opioid receptor involvement in nitrous oxide analgesia in mice.

This study was undertaken to assess the sensitivity of nitrous oxide (N2O) analgesia to antagonism by intrathecally (IT) and intracerebroventricularly (ICV) administered antagonists selective for kappa- and mu-opioid receptors. Male ICR mice were pretreated IT or ICV with the kappa antagonist nor-binaltorphimine (nor-BNI), 1 or 50 nmol, respectively, or distilled water (control), then exposed to N2O (50% or 75% in oxygen). Compared with IT control mice, IT nor-BNI-pretreated mice responded with significantly less analgesia. Compared with ICV control mice, ICV nor-BNI-pretreated mice also showed markedly reduced analgesic response. Other mice were pretreated IT or ICV with either the selective and irreversible mu antagonist beta-funaltrexamine (beta-FNA, 5.0 micrograms) or distilled water (control). When exposed to N2O 24 h later, beta-FNA-pretreated and control mice exhibited comparable analgesic responses. These preliminary results suggest that N2O analagesia in mice may involve spinal and supraspinal kappa-opioid receptors but not mu-opioid receptors.

Analgesia↗

PubMed1989

Interaction between nitrous oxide and diazepam in the mouse staircase test.

The interaction between nitrous oxide and diazepam was assessed in the mouse staircase test. In this paradigm, the numbers of rears (NR) (simultaneous standing on hindlegs and sniffing the air) and steps ascended (NSA) reflect anxiety and locomotor activity, respectively. Antianxiety drugs characteristically reduce NR but not NSA, while sedative drugs reduce both NR and NSA in generally parallel fashion. In this study, increasing concentrations of nitrous oxide alone produced progressively greater and statistically significant increases in NSA. Nitrous oxide alone had no significant effect on NR until, at a concentration of 75%, it decreased NR. Diazepam alone decreased NR equally and significantly at all doses. With certain combinations of concentration and dose, nitrous oxide enhanced the effect of diazepam on NR without altering NSA. These findings suggest that nitrous oxide can increase the antianxiety effect of diazepam without increasing its sedative effect in the mouse staircase paradigm.

Animals↗