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R M Quock

Publications and source records attributed to R M Quock.

At least 55 records · Page 3Linked to original sources
PubMed1988

Influence of narcotic antagonist drugs upon nitrous oxide analgesia in mice.

Nitrous oxide produced a concentration-related suppression of phenylquinone-induced abdominal constriction in mice. This analgesic effect was significantly reduced (but not abolished) by systemic pretreatment with (-)-naloxone or naltrexone but not (+)-naloxone. Systemic pretreatment with methylnaltrexone failed to appreciably influence nitrous oxide analgesia; however, methylnatrexone, administered centrally, significantly attenuated the drug effect. Furthermore, nitrous oxide analgesia was significantly reduced by MR-2266 (which is relatively selective for kappa-opioid receptors) but not by beta-funaltrexamine (which is selective for mu-opioid receptors) at the doses employed in this study. These findings suggest that nitrous oxide analgesia might involve an activation of kappa-opioid receptors in the central nervous system; however, a possible involvement of mu-opioid receptors is not absolutely precluded by this study.

Analgesia↗
PubMed1988

Central pharmacological activity of a quaternary ammonium compound in streptozotocin diabetic mice.

Possible changes in blood-brain barrier (BBB) function as a result of diabetes were investigated by assessing antagonism of morphine analgesia in diabetic mice by methylnaltrexone (MeNTX), an opioid receptor blocker that does not cross the BBB when administered subcutaneously (SC). In streptozotocin (STZ)-treated diabetic mice--but not vehicle-treated, non-diabetic mice--treatment with SC MeNTX significantly reduced morphine analgesia. In vehicle-treated, non-diabetic mice, morphine analgesia was antagonized by MeNTX administered intracerebroventricularly and by SC naltrexone, which crosses the BBB. Reduction of STZ-induced hyperglycemia by insulin reversed the effectiveness of SC MeNTX in antagonizing morphine analgesia. We hypothesize that in STZ diabetic mice, MeNTX was able to cross the BBB and block brain opioid receptors.

Animals↗
PubMed1988

Enhanced apomorphine-induced hypothermia in alloxan-treated rats.

Previous studies have indicated that drug-induced experimental diabetes is associated with increased receptor binding in the rat brain. The purpose of this study was to determine whether the dopamine receptor agonist apomorphine (APO) might produce an accentuated hypothermic response in rats rendered diabetic by alloxan (ALX) treatment. In a previous study, however, the only controls used were ALX-treated rats that failed to develop glycosuria. Therefore, in this study, APO (0.5 mg/kg IP) was administered to ALX-diabetic and non-diabetic as well as saline-treated control rats to ascertain whether the APO responsiveness of ALX-non-diabetic rats was comparable to that of saline control animals. ALX-diabetic rats experienced significantly greater hypothermic response to APO than did the saline control animals. Although ALX-non-diabetic rats were similar to the saline control animals in body weight and blood glucose levels, they too were hyperresponsive to APO. These findings indicate that pancreatic injury from ALX, while not always sufficiently severe to produce overt diabetes, does appear to induce an hyperresponsiveness to APO-induced hypothermia in a manner similar to that observed in severely diabetic animals.

Alloxan↗
PubMed1987

Nitrous oxide-induced hypothermia in the rat.

Exposure of rats to high levels of nitrous oxide (N2O) in oxygen (O2) reduced body temperature in a concentration-related manner. The hypothermia was partly reversed by pretreatment with naloxone but not naltrexone. But in rats rendered tolerant to morphine by pellet implantation, exposure to 75% N2O/25% O2 evoked a marked hypothermia similar to that observed in morphine-naive animals. In another experiment, the hypothermic effect of chloral hydrate was also sensitive to antagonism by pretreatment with naloxone but not naltrexone. These observations lead us to suspect that N2O-induced hypothermia in rats is possibly not mediated by opiate receptors. The thermotropic activity of N2O may result from some non-opioid action of N2O. Its selective antagonism by naloxone (but not naltrexone) may be due to a unique non-opioid analeptic action of naloxone.

Animals↗
PubMed1987

Microwave facilitation of domperidone antagonism of apomorphine-induced stereotypic climbing in mice.

The dopaminergic agonist apomorphine produced dose-dependent stereotypic climbing behavior in mice housed in cages with vertical bars. This drug effect was competitively inhibited by systemic pretreatment with the centrally acting dopaminergic antagonist haloperidol but not by microwave irradiation (2.45 GHz, 20 mW/cm2, CW, 10 min) nor by systemic pretreatment with domperidone, a dopaminergic antagonist that only poorly penetrates the blood-brain barrier (BBB). Yet when mice were systemically pretreated with domperidone and then subjected to microwave irradiation (as above), the apomorphine effect was significantly reduced. Microwave irradiation also facilitated antagonism of the apomorphine effect by low and otherwise ineffective systemic pretreatment doses of haloperidol. Apomorphine-induced stereotypic climbing behavior was also reduced by domperidone administered intracerebrally, which bypassed the BBB. Exposure of intracerebral domperidone-pretreated animals to microwave irradiation failed to increase the degree of antagonism. These findings indicate that microwave irradiation can facilitate central effects of domperidone, a drug which acts mainly in the periphery. One possible explanation for these findings is that microwave irradiation alters the permeability of the BBB and increases the entry of domperidone to central sites of action.

Animals↗
PubMed1987

Comparison of nitrous oxide, morphine and diazepam effects in the mouse staircase test.

Mice were exposed for 10-20 min to room air, 100% oxygen (O2) or increasing concentrations of nitrous oxide (N2O) in O2, then tested for 3 min in a staircase inside a glovebag. N2O produced a concentration-dependent increase in the number of steps ascended (NSA) but no change in the number of rears (NR). Pretreatment with naloxone reversed the increase in NSA and also unmasked N2O reduction in NR. By comparison, increasing doses of the narcotic standard morphine reduced NSA and NR; these changes in NSA and NR were sensitive to antagonism by naloxone. The benzodiazepine standard diazepam produced a dose-related reduction in NR while reducing NSAd only at higher doses. These data indicate that N2O influences on NSA and NR resemble neither morphine nor diazepam. In addition, it appears that the opioid activity of N2O might mask its antianxiety activity in this particular paradigm.

Animals↗
PubMed1987

Rearing and step climbing behavior of X-linked hypophosphatemic (Hyp) mice.

Hyp mice are a model for X-linked hypophosphatemia, the most common form of vitamin D-resistant rickets. Previous reports indicate alterations in the nervous system of these mice. The present study examined rearing and step climbing behavior in Hyp mice in the staircase test. We found that male Hyp mice have large reductions in both the number of rears and steps climbed when compared to normal male mice. When compared to normal female mice, female Hyp mice have a small reduction in the number of steps climbed but no significant reduction in the number of rears. However, they have greater rearing and climbing activity than male Hyp mice. These reductions in activity are not correlated with the severity of bone disease. Gonadectomy had no effect on activity in male mice but reduced activity comparably in both Hyp and normal female mice. We conclude that Hyp mice have altered behavior in the staircase test and that the magnitude and type of the alteration is influenced by the sex of the animal.

Animals↗
PubMed1987

Modification of an infant incubator for exposure of experimental animals to nitrous oxide.

Research with N2O is hampered because it is a gas and must be inhaled by the test subject rather than injected. Described herein is the development of a practical and efficient exposure chamber for such research. A Model C-35 Isolette infant incubator was modified by installation of a manifold system for distribution and opposed-suction fans for a circulation of the gas mixture (N2O in oxygen). An exponential model was developed, predicated on gas concentration uniformity, to track the increasing concentration of N2O during chamber filling and to predict the time required for the chamber to assume a steady-state level of N2O. This model requires that three things be known: the volumetric flow rate of administered gas mixture, the concentration of N2O in that mixture, and the volume of the chamber. The model predicts that X(t)/X infinity = 1 - exp(-t/tau), where X(t) is the concentration of N2O of an instant t; X infinity, the concentration of N2O administered; and tau, the time constant--the ratio of chamber volume to volumetric flow rate. This model was confirmed via mass spectroscopy analysis of gas from the chamber during filling.

Air↗
PubMed1987

Kinetic modeling of hormone release: application to time-averaged met-enkephalin release.

The time course of hormone concentrations in response to a stimulus can be characterized with kinetic methods to express rates of hormone release and elimination, total amount of hormone release and expected best times for blood sampling. Routine application of kinetic methods should increase the sensitivity and applicability of hormonal challenge tests. Applications to the TRH test and to prolactin release measurements are reviewed. A new kinetic model for continuously collected samples is applied to measurements of met-enkephalin release in rats. Calculations indicated an initial concentration of 1876 pg/ml and a ventricular volume of distribution of 0.25 ml. After exposure of rats to nitrous oxide, the rate of release of met-enkephalin-like activity into the ventricles rose from 3.4 to 8.3 pg/min.

Animals↗
PubMed1986

Influence of naloxone upon apomorphine-induced rotational behavior in rats with electrolytic versus chemolytical lesions of the substantia nigra.

In rats with unilateral electrolytic lesions of the substantia nigra, apomorphine induced ipsilateral rotational behavior that was significantly potentiated by naloxone. Yet, in rats with unilateral chemolytic (6-hydroxydopamine) lesions of the substantia nigra, apomorphine induced dose-dependent contralateral turning that was not influenced by pretreatment with even high doses of naloxone. High performance liquid chromatographic analysis of corpora striata from these rats revealed electrolytically-lesioned animals to have a 60-70% reduction in dopamine content while chemolytically-lesioned animals were virtually completely depleted of dopamine. These results suggest that striatal dopamine may be required for naloxone potentiation of apomorphine-induced effects in the rat rotational behavior paradigm.

Animals↗
PubMed1986

Influence of nitrous oxide upon regional brain levels of methionine-enkephalin-like immunoreactivity in rats.

The influence of a 60-min exposure to 75% nitrous oxide/25% oxygen upon concentrations of methionine-enkephalin-like immunoreactivity (MELI) in discrete brain regions was investigated in conscious rats. Compared to room air-exposed control animals, nitrous oxide-exposed rats had 12-18% increases in MELI in the brainstem, spinal cord, hypothalamus and corpus striatum. There were no significant differences between control and nitrous oxide-exposed rats in levels of MELI in the cerebral cortex or diencephalon.

Animals↗
PubMed1986

Microwave facilitation of methylatropine antagonism of central cholinomimetic drug effects.

Pilocarpine-induced hypothermia and oxotremorine-induced tremors in mice are central cholinomimetic drug effects that are readily blocked by the muscarinic antagonist atropine. However, the quaternary ammonium derivative of atropine, methylatropine, is unable to block these cholinomimetic drug effects by virture of its inability to penetrate the blood-brain barrier (BBB) and blood-cerebral spinal fluid barrier (B-CSFB). Dose-response curves for pilocarpine and oxotremorine effects are not appreciably affected either by pretreatment with methylatropine (1.0 mg/kg) or by exposure to moderate-level microwave irradiation (2.45 GHz, 23.7 W/kg, CW, 10-min exposure). However, in mice receiving both the methylatropine pretreatment and microwave irradiation, the dose-response curves for both pilocarpine and oxotremorine effects were significantly shifted to the right, signifying a central anticholinergic action by methylatropine. These data indicate that a single acute exposure to a thermogenic level of microwave irradiation facilitates methylatropine antagonism of centrally mediated cholinomimetic drug effects. One possible explanation for this observation is that microwave radiation may enhance passage of quaternary ammonium compounds like methylatropine across the BBB and B-CSFB.

Animals↗
PubMed1985

Narcotic antagonist-induced hypotension in the spontaneously hypertensive rat.

Intravenous naloxone or naltrexone produced transient, dose-related reductions in the mean arterial pressure (MAP) and heart rate (HR) of urethane-anesthetized spontaneously hypertensive rats (SHRs). Yet these same doses of narcotic antagonists reduced HR but not MAP of normotensive Wistar-Kyoto rats (WKYs). Such effects were not observed upon administration to SHRs of increasing doses of methylnaltrexone, which possesses no central activity. (+)-Naloxone, which does not block opiate receptors, reduced HR but not MAP of both SHRs and WKYs. These findings indicate that SHRs and WKYs differ in their MAP and HR responses to narcotic antagonists. The high doses required for effect plus the brevity of the responses suggest that these drug effects are perhaps not mu-opiate receptor-mediated; however, the methylnaltrexone and (+)-naloxone findings clearly implicate a central specificity of action. We conclude that narcotic antagonist-induced changes in MAP and HR in SHRs are possibly specific and central in origin yet not mediated by mu-opiate receptors.

Animals↗
PubMed1985

Narcotic antagonist potentiation of apomorphine drug effect: a stereospecific, centrally mediated drug action.

Systemic pretreatment with naloxone but not its (+)-enantiomer significantly potentiated apomorphine-induced stereotypic climbing activity in mice. Systemic or central pretreatment with naltrexone also significantly potentiated the apomorphine drug effect. The N-methyl derivative of naltrexone had no influence when administered systemically but significantly potentiated the apomorphine drug effect when administered centrally. These findings suggest that narcotic antagonist potentiation of apomorphine-induced stereotypic climbing in mice is a stereospecific phenomenon that originates in the central nervous system.

Animals↗
PubMed1985

Sex and strain differences in morphine-induced temperature effects in WKYs and SHRs.

Male and female normotensive Wistar-Kyoto rats (WKYs) and spontaneously hypertensive rats (SHRs) all responded to morphine treatment with biphasic dose-response curves, exhibiting hyperthermia at low doses and hypothermia at higher doses. However the direction and magnitude of temperature changes induced by different doses of morphine varied significantly depending upon the sex and strain (WKY vs. SHR) of the test animals. Both WKY and SHR males responded with little change in temperature at 1.0 mg/kg and hyperthermia at 5.0 mg/kg. Hypothermia appeared in SHR males at 10 mg/kg, while hypothermia in WKY males was not seen until 20 mg/kg was administered. Both WKY and SHR females demonstrated a greater sensitivity than their male counterparts to the thermotropic effects of morphine, exhibiting hyperthermia at 1.0 mg/kg, which was greater than the hyperthermia exhibited by male rats, and progressively greater hypothermia at 2.0, 5.0 and 10 mg/kg. SHR females demonstrated hypothermia at lower doses of morphine than did WKY females but were otherwise not different. These findings indicate that (1) morphine-induced temperature effects in SHRs and WKYs are dependent upon dose; (2) SHRs seem more sensitive than WKYs to the hypothermic effects of morphine; and (3) female rats seem more sensitive than male rats to the thermotropic effects of morphine in general.

Animals↗
PubMed1985

Does nitrous oxide induce release of brain opioid peptides?

Increased concentrations of immunoreactive methionine-enkephalin but not leucine-enkephalin were measured in fractions of cerebrospinal fluid perfusate collected from ventricular-cisternally perfused, urethane-anesthetized rats exposed to a mixture of 75% nitrous oxide/25% oxygen for 60 min. These findings suggest that nitrous oxide might be capable of inducing the release of methionine-enkephalin in the central nervous system.

Animals↗