SEARCH · PubMed Health

Results for “Reflex, Righting”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 685 records · Page 38Linked to original sources

PubMed1986

Prolonged hypothermia after phenobarbital-induced anesthesia in adrenalectomized rats.

Adrenalectomized rats are hypersensitive to the hypothermic as well as hypnotic effects of phenobarbital. The exaggerated hypnotic response is more pronounced in the chronic (10 day) than the acute (1 day) adrenalectomized rat and is reversed by glucocorticoid replacement. The prolonged hypothermia to a hypnotic dose of phenobarbital occurs in adrenalectomized but not adrenodemedullated rats. This hypersensitivity is characterized by an impaired ability to regain normal body temperatures for as long as 24 hours after regaining the righting reflex. The prolonged hypothermia is prevented by prior treatment with glucocorticoids but not mineralocorticoids. There appears to be no gross alteration in disposition of phenobarbital following adrenalectomy suggesting that the prolonged duration of hypothermia is not a consequence of accumulation of the drug.

Adrenalectomy↗

PubMed1986

Effects of postnatal caffeine exposure through dam's milk upon weanling rats.

The effects of postnatal caffeine exposure received through mother's milk were examined in rat pups by administering 0.0125 or 0.05% caffeine solution to the dams throughout lactation. Offspring of caffeine-treated dams showed significantly earlier onset of auditory startle and air righting reflexes. No direct effects of treatment were observed on eight measures of open field activity. At weaning, high-dose caffeine pups exhibited a transient increase in caffeine acceptance in two-bottle taste preference tests and showed cyclic exaggerations in caffeine preference-aversion functions which persisted throughout the 22-day postweaning test period. The caffeine levels in the dams' milk had a 30-fold daily fluctuation reflecting the fluid ingestion pattern related to the light-dark cycle and caffeine elimination rate. Caffeine concentrations in the brains of the pups varied between 0.01 and 9.0 micrograms/g.

Animals↗

PubMed1987

Effect of muscimol on ethanol-induced central nervous system depression.

In male Sprague-Dawley rats acute ethanol (1.0 and 2.0 g/kg) produced impairment of motor coordination and induced hypnosis (4.0 g/kg). Muscimol (1.25 mg/kg, IP) prior to ethanol administration enhanced motor impairment as measured by the aerial righting reflex. The rate of ethanol disappearance from the blood was unaltered by muscimol. Functional tolerance to the effect of ethanol on sleep time was produced by a 24 hr ethanol inhalation procedure. Animals tested 48 hr after ethanol inhalation exhibited a reduced sleep time from ethanol (4.0 g/kg). Muscimol (1.75 mg/kg) was administered along with ethanol 48 hr following 1 day of ethanol inhalation. Although the animals exhibited tolerance to ethanol-induced hypnosis, they did not manifest tolerance to the effect of muscimol.

Animals↗

PubMed1987

Reversal of opioid-induced muscular rigidity in rats: evidence for alpha-2 adrenergic involvement.

Compounds from several different pharmacological classes were tested for their ability to reverse the muscular rigidity induced by an intravenous dose of fentanyl that also caused loss of the righting reflex (LOR). Opioid antagonists reversed the entire syndrome--LOR and rigidity but, generally, rigidity could be reversed nonspecifically by doses of compounds that caused LOR by themselves (e.g., CNS depressants). Muscle relaxants and agonists of histamine, which appeared to be acting peripherally, were also effective. On the other hand, serotonergic drugs and dopamine agonists were not. However, dopaminergic antagonists with adrenolytic activity (i.e., chlorpromazine, haloperidol) reversed rigidity, whereas sulpiride did not. Moreover, rigidity reversed by neuroleptics could be restored by piperoxane, an alpha-2 adrenergic antagonist. In addition, clonidine and other alpha-2 agonists selectively reversed only rigidity following systemic or central administration at doses several orders of magnitude lower than other compounds tested. It is proposed that opioid-induced rigidity is reversed by inhibition of sympathoadrenal outflow which can be accomplished selectively, centrally, by alpha-2 agonists.

Adrenergic alpha-Agonists↗

PubMed1987

Effects of intraseptal drug administration on pentobarbital-induced narcosis and hippocampal choline uptake.

Effects of injection of drugs into the septum on pentobarbital anesthesia were investigated in the rat. Intraseptal microinjection of bicuculline (5 micrograms), arecoline (2 micrograms), and phenylephrine (5 micrograms) shortened, MK-212 (5 micrograms) prolonged, and atropine (2 micrograms) had no significant effect on the duration of pentobarbital-induced loss of righting reflex. Bicuculline and arecoline increased and MK-212 reduced hippocampal cholinergic activity as measured by change in hippocampal sodium-dependent high-affinity choline uptake after intraseptal drug injection. It is concluded that activation of the septal-hippocampal cholinergic pathway might be an important neuromechanism for recovery from pentobarbital-narcosis.

Animals↗

PubMed1988

Prevention of soman toxicity after the continuous administration of physostigmine.

Protective effects of continuous administration of physostigmine alone, or in addition to scopolamine, against soman-induced toxicity were studied in guinea pigs. The results clearly demonstrated that treatment with physostigmine continuously via implanted mini-osmotic pumps for 4 or 7 days prior to soman exposure significantly protected from soman-induced mortality. In vehicle-infused guinea pigs, tremors, convulsions and loss of righting reflex occurred prior to their deaths induced by soman. Although all of the guinea pigs which received physostigmine pretreatment for 4 days prior to soman administration also displayed soman-induced tremors and convulsions, the onsets of these symptoms were significantly delayed. When animals continuously treated with physostigmine received injections of scopolamine 10 min prior to soman injections, there was a decreased incidence of all three toxicity symptoms as well as an increase in the latency to onset of tremors. Scopolamine was also able to reverse toxicity symptoms when soman was administered earlier. In animals which had been continuously treated with physostigmine via mini-osmotic pumps, the protective action against soman-induced toxicity was still apparent. On the contrary, acute physostigmine administration failed to protect against soman lethality. The present results suggest that the prophylactic uses of physostigmine via mini-osmotic pumps might be more useful than the acute bolus administration of physostigmine.

Acetylcholinesterase↗

PubMed1988

Codeine produces a cholinergically mediated analeptic effect in rats and rabbits.

The intravenous administration of codeine to diazepam-narcotized rabbits resulted in a shortened duration of loss of righting reflex. Coadministration of naltrexone plus codeine enhanced this analeptic effect and was also effective in shortening the duration of pentobarbital narcosis. The analeptic effect was blocked by atropine, but not by methylatropine, indicating involvement of a central cholinergic mechanism. In rats the analeptic activity correlated with the reversal of the diazepam-induced fall in sodium dependent high affinity choline uptake in hippocampal and cortical synaptosomes. These findings may represent the pharmacological basis of the recently reported antinarcoleptic action of codeine in man.

Animals↗

PubMed1989

Development of ethanol tolerance not altered by 6-OHDA lesions of dorsal bundle.

It has been demonstrated via intraventricular (IVT) 6-OHDA infusions that central nervous system norepinephrine is necessary for the development of tolerance to ethanol (ETOH) in the mouse. Because 6-OHDA IVT infusions are not specific, we tested the effects of destruction of a specific NE pathway on development of ETOH tolerance. Rats received 6-OHDA lesions of the dorsal noradrenergic bundle (DB) and the development of ethanol tolerance was measured using the sleeptime test. The time between loss and recovery of the righting reflex was determined after an acute challenge dose of ETOH. Rats were than placed on ETOH diet for 13 days followed by a repeat of the sleeptime test. Sham and 6-OHDA-DB-lesioned rats exhibited the same sleeptime prior to ETOH diet, consumed similar amounts of ETOH diet over the course of 13 days, and exhibited similar significantly (p less than 0.0005) shorter sleeptimes after ETOH diet. Our data suggest that destruction of the DB does not alter development of ETOH tolerance as measured by the sleeptime test.

Animals↗

PubMed1989

Pentobarbital-induced hyperactivity in mice: negligible role of opioid mechanisms.

Subhypnotic doses (10 and 20 mg/kg) of pentobarbital significantly elevated locomotor activity measured for 30 min in CD-1 mice. The hyperactivity was also observed in mice recovering from pentobarbital-induced (50 mg/kg) sleep (measurements starting 15 min after recovery of righting reflex). Naloxone in doses up to 4 mg/kg did not affect significantly the pentobarbital-induced hyperactivity in any experiment; a dose of 8 mg/kg only partially attenuated the hyperactivity induced by a dose of 20 mg/kg of pentobarbital, but did not affect significantly either the stimulatory effect of a low subhypnotic dose (10 mg/kg) or the posthypnotic hyperactivity. This suggests a negligible involvement of opioid mechanisms in the hyperactivity induced by pentobarbital.

Animals↗

PubMed1990

Differential actions of RO 15-1788 and diazepam on poikilothermia, motor impairment and sleep produced by ethanol.

In adult male Sprague-Dawley rats kept at an ambient temperature of 23-25 degrees C, ethanol was injected intraperitoneally in a dose of 4.0 g/kg to produce a clear-cut impairment of autonomic and motorial functions. Following the injection of ethanol, motor coordination, measured on a rotorod, behavioral sleep, righting reflex and colonic temperature were monitored at predetermined intervals for 5.0-7.0 hr. In the first experiment, either 1.0 mg/kg RO 15-1788 (flumazenil), a benzodiazepine (BZ), receptor antagonist, or 1.0-5.0 mg/kg diazepam, a classical benzodiazepine receptor agonist, were injected intraperitoneally either alone or concurrently with ethanol's administration. In the second study, either RO 15-1788 (1.0 or 2.0 mg/kg) or diazepam (1.0 or 5.0 mg/kg) was injected at the nadir of the fall of body temperature induced by ethanol. Although RO 15-1788 alone failed to affect the rats' temperature, it did not prevent the characteristic ethanol-induced hypothermia but rather potentiated it in a dose-dependent manner. Further, this BZ receptor antagonist exacerbated motor incoordination and other behavioral effects when given either simultaneously with ethanol or at the nadir in the animals' core temperature. Although diazepam evoked a dose-dependent hypothermia, it did not enhance ethanol-induced hypothermia when both drugs were administered simultaneously. However, diazepam augmented motor incoordination and other effects and served to delay their recovery. When given to the rats at the nadir of ethanol hypothermia, diazepam did not potentiate ethanol's thermolysis but retarded the recovery from hypothermia; it caused also a dose-dependent delay in the recovery of motor coordination and other responses.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

The noncompetitive N-methyl-D-aspartate antagonists, MK-801, phencyclidine and ketamine, increase the potency of general anesthetics.

The potency of general anesthetics from different chemical classes was tested after pretreatment with subanesthetic doses of noncompetitive N-methyl-D-aspartate (NMDA) antagonists in mice. Changes in general anesthetic potency were assessed by determination of alteration of duration of loss of righting reflex for ethanol and pentobarbital and changes in the minimum alveolar concentration (MAC) for the volatile anesthetics, halothane and diethyl ether. The ability of the noncompetitive NMDA antagonists, MK-801 [(+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine ], phencyclidine (PCP) and ketamine, to increase the potency of general anesthetics paralleled their potency as NMDA antagonists and their affinity for the PCP receptor site of the NMDA receptor-ionophore complex (MK-801 greater than PCP greater than ketamine). These results indicate that block of central NMDA receptors may contribute to the production of anesthesia by a variety of agents.

Anesthesia, General↗

PubMed1990

Pentobarbital tolerance and withdrawal: correlation with effects on the GABAA receptor.

A model for the development of pentobarbital tolerance and dependence was characterized and correlated with changes in radioligand binding to the GABAA-benzodiazepine receptor chloride channel complex. While one day of pentobarbital exposure decreased the duration of loss of righting reflex, tolerance to the hypothermic effects of thiopental and barbital took 7 days to develop, indicating that pharmacokinetic and pharmacodynamic tolerance are separable. Increased sensitivity to pentylenetetrazol-induced seizures was first observed after 3 days of pentobarbital exposure, suggesting brain areas involved in seizure control develop tolerance to, and dependence on pentobarbital faster than those involved in temperature regulation. Acute exposure to pentobarbital in vivo did not affect cortical binding of [3H]muscimol in vitro, while tolerance caused a decrease in binding due to an increase in the low-affinity site KD. Pentobarbital tolerance also caused a decrease in the cortical binding of the benzodiazepine, [3H]flunitrazepam. These observations suggest that the acute effects of barbiturates on the GABAA receptor complex are reversible, while tolerance causes receptor modifications which may be related to the development of physical dependence.

Animals↗

PubMed1990

Cocaine produces cholinergically mediated analeptic and EEG arousal effects in rabbits and rats.

Cocaine (1-5 mg/kg, IV) shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was completely blocked by scopolamine (1 mg/kg, IV), but not by scopolamine methylbromide, suggesting that a central cholinergic mechanism was involved. In urethane-anesthetized rats cocaine (1 mg/kg, IV) consistently generated hippocampal EEG theta rhythm lasting about 40 min. This effect was also abolished by scopolamine. These results suggest that cocaine produced behavioral and EEG arousal responses that involved the septohippocampal cholinergic system.

Acetylcholine↗

PubMed1990

Effects of two benzodiazepine inverse agonists, RO 15-4513 and FG 7142, on recovery from pentobarbital and halothane anesthesia in the rat.

A new class of drugs, the benzodiazepine inverse agonists, have recently been shown to antagonize some of the behavioral and sedative effects of benzodiazepines, barbiturates, and alcohol. Preliminary studies suggested that at least one of these drugs, RO 15-4513, may also be able to reverse the general anesthetic properties of volatile halogenated agents. Another inverse agonist, FG 7142, exhibits a similar ability to antagonize alcohol or benzodiazepines. However, FG 7142 is less potent than RO 15-4513 and has less affinity for the benzodiazepine receptor (BZR). The present studies were therefore undertaken to compare the analeptic effects and relative potencies of RO 15-4513 and FG 7142 on the anesthetic properties of pentobarbital compared with the general anesthetic agent halothane as measured by the time for recovery of the righting reflex in the rat. Three basic experimental paradigms were employed. Drug (FG or RO) or carrier was administered 5 minutes prior to the induction of pentobarbital anesthesia. Drug or carrier was administered to anesthetized animals 60 minutes after pentobarbital injection. Lastly, drug or carrier was administered 5 minutes prior to 15 minutes of halothane anesthesia. In addition, the selective benzodiazepine antagonist, flumazenil (RO 15-1788), was used to determine if the effects of the benzodiazepine inverse agonists on recovery from barbiturate or halothane anesthesia were due to activity at the BZR. The results revealed that RO was both more potent and more effective than FG at speeding recovery from barbiturate anesthesia in the rat. RO's effects appeared to be primarily due to BZR inverse agonist activity since it could be reversed by the BZR antagonist, flumazenil.(ABSTRACT TRUNCATED AT 250 WORDS)

Anesthesia Recovery Period↗

PubMed1991

Ethanol-induced depression of aggression in mice antagonized by hyperbaric exposure.

The present study investigated the effect of hyperbaric exposure on ethanol-induced depression of aggressive behavior measured by resident-intruder confrontations. Adult male CFW mice (residents) were paired with females and housed together for 26 days. Then, resident mice were intubated with either ethanol (2 g/kg) or water (20 ml/kg) and were exposed to 1 atmosphere absolute (ATA) air, 1 ATA helium oxygen (heliox) or 12 ATA heliox using a within-subjects counterbalanced design. Thirty minutes after intubation an intruder was introduced. Ethanol significantly decreased aggressive behaviors (attack latency, attack bites, sideways threats, tail rattles and pursuit) in 1 ATA-treated animals. Pressure completely antagonized the depression of aggression induced by ethanol. Ethanol alone and pressure alone did not significantly affect nonaggressive behaviors. There were no statistically significant differences between groups in blood ethanol concentrations 50 minutes after intubation. These results suggest that ethanol's effects on aggressive behavior result from the same membrane actions leading to loss of righting reflex, depression of locomotor activity, tolerance and dependence.

Aggression↗

PubMed1991

Attenuation of central alpha 2 adrenergic action in diabetic rats.

Molecular components in transmembrane signaling may be dysfunctional in insulin-deficient states. To investigate whether the alpha 2 adrenergic receptor-effector mechanism is functionally altered by insulin deficiency, we determined the hypnotic response to dexmedetomidine [(+)4-[1-(2,3-dimethylphenyl)ethyl]-1H-imidazole, a highly-selective alpha 2 agonist, in streptozotocin-induced diabetic rats. The duration of the loss of righting reflex (sleep time) in response to dexmedetomidine, 0.25 mg.kg-1 IP, was measured in rats pretreated with streptozotocin, 50 mg.kg-1 IP. Dexmedetomidine sleep time was significantly shortened when tested 10 days (-25%), 3 (-29%), 6 (-35%) and 8 (-47%) weeks into the diabetic state. Supplementation of the diabetic rats with insulin normalized alpha 2 responsiveness. Acute hyperglycemia did not reduce dexmedetomidine-induced sleep time. Sleep time was also reduced when dexmedetomidine was administered via the intracerebroventricular (ICV) route at 4 (-21%) and 8 (-29%) weeks after streptozotocin. Thus the central nervous system response to the alpha 2 adrenergic agonist has become attenuated. The mechanism may involve a perturbation of an insulin-sensitive molecular component of the signal transduction pathway responsible for alpha 2 adrenoceptor-mediated anesthetic action.

Adrenergic alpha-Agonists↗

PubMed1991

D-1 agonist, SKF 38393, but not a D-2 agonist, produces a cholinergically mediated analeptic effect in rabbits.

SKF 38393 (2-15 mg/kg, IV), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was blocked by atropine (2-5 mg/kg, IV), but not by atropine methylbromide, suggesting that a central cholinergic mechanism was involved. The analeptic effect was also blocked by SCH 23390 (0.1 mg/kg, IV) or raclopride (5 mg/kg, IV). These results indicate that SKF 38393 activates central cholinergic neurons, which in turn initiate the analeptic effect. However, the fact that raclopride also blocked the SKF 38393 analeptic effect, but quinpirole did not exert any analeptic effect, suggests that a D-1/D-2 modulation of cholinergic systems may be involved in the SKF 38393-induced analeptic effect. These results also support our earlier findings and view that cocaine-induced analeptic activity is mediated by a dopaminergic-cholinergic mechanism.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1991

Neurotoxic effects of secalonic acid D in mice during subchronic postnatal exposure.

To establish a dose-response of neurotoxic effects to daily oral doses of the mycotoxin secalonic acid D (SAD), as well as to correlate the neonatal behavioral responses to smaller doses of SAD with the attendant neurochemical effects in mice, 5 neonates of each sex were placed with each mother and 4 litters were treated orally with 0 to 5 mg/kg of SAD daily from postnatal day (PND) 3 through 35. Body weights, toxic signs, and mortality were used to arrive at no observable effect level (NOEL). Performance in several behavioral tests and changes in regional norepinephrine and dopamine levels in the brains of neonates treated with SAD at NOEL (1.25 mg/kg/day) or below were evaluated at selected times during SAD exposure. Doses as low as 1.25 mg/kg/day reversibly reduced body weights in both sexes on PND 12 and 13 compared to controls, whereas doses of 2.5 mg/kg/day or greater were lethal (LD50 of 2.5 mg/kg/day). Toxic signs observable in neonates receiving 2.5 mg/kg/day or more of SAD included fine body tremors, uncoordinated movements, hindlimb weakness, circling, loss of righting reflex, paddling, and terminal coma. Ontogeny of cliff avoidance (PND 5, 7, and 9), hindlimb grip response (PND 14, 17, and 20), olfactory discrimination (PND 8 through 11) and swimming (PND 13 through 21) were significantly delayed by SAD exposure: some even at 0.625 mg/kg/day. Dopamine levels significantly increased on PND 13 and decreased on PND 20 only in the olfactory lobe of SAD-exposed neonates. Norepinephrine levels were unchanged in all the brain regions examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗