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Biomedical subjects

W G Clark

Publications and source records attributed to W G Clark.

At least 55 records · Page 3Linked to original sources
PubMed1982

Depression of learned thermoregulatory behavior by central injection of opioids in cats.

Third cerebral ventricular administration of morphine (20 microgram), pentazocine (1 mg) or the synthetic opioid peptides D-Ala2-Met-enkephalinamide (25 microgram) and D-Ala2-D-Leu5-enkephalin (10 microgram) decreased heat-reinforcement activity and either reduced or did not increase heat-escape activity of cats trained to control thermal stimuli through behavior. If the behavioral changes had been coupled to the primary effects of these opioids on thermoregulation, one would have expected an inverse relationship between changes in heat-reinforcement and heat-escape activity. Motor incapacitation appeared not to have contributed to the reduction in responding except briefly after pentazocine injection. The opioids may have distracted the animals or otherwise reduced their reaction to thermal stimuli until body temperature increased to a potentially dangerous level.

Animals↗
PubMed1982

Extreme hyperthermia induced in cats by the enkephalin analog FK 33-824.

FK 33-824 [H2N-Tyr-D-Ala-Gly-MePhe-Met(O)-OH] was injected into the third cerebral ventricle of unrestrained cats. Doses of 0.25-4 microgram induced dose-related increases in body temperature. Hyperthermic responses to 1 microgram of the peptide were greater the warmer the environment. Naloxone given intraventricularly 1 hr after FK 33-824 (1 microgram) reduced the hyperthermia. In 12 tests with six cats FK 33-824 (1-25 microgram) increased temperature 4.2-4.7 degrees C. These marked responses were also inhibited by naloxone, but two cats died when administration of antagonist was delayed for 80 min to 3 hr after attainment of maximal body temperature. Larger doses of FK 33-824 (50-250 microgram) evoked little increase in temperature, indicative of a separate action to depress thermoregulation. Although responses to FK 33-824 were antagonized by naloxone, this peptide, like another enkephalin analog D-Ala2-Met-enkephalinamide, must act on receptors which are not affected by morphine since (1) the hyperthermic response to FK 33-824 varied with environmental temperature, whereas the response to morphine does not, and (2) high doses of FK 33-824 depressed thermoregulation, an activity not shared by morphine in the cat. Furthermore, the maximal increases in temperature after FK 33-824 injection were greater than those evoked by either morphine or D-Ala2-Met-enkephalinamide. This observation provides evidence for an additional subset of naloxone-sensitive, v, receptors, stimulation of which can influence thermoregulation in the cat.

Animals↗
PubMed1981

Changes in body temperature after administration of antipyretics, LSD, delta 9-THC, CNS depressants and stimulants, hormones, inorganic ions, gases, 2,4-DNP and miscellaneous agents.

This survey concludes a series of complications of data from the literature, primarily published since 1965, on thermoregulatory effects of antipyretics in afebrile as well as in febrile subjects, LSD and other hallucinogens, cannabinoids, general CNS depressants, CNS stimulants including xanthines, hormones, inorganic ions, gases and fumes, 2,4-dinitrophenol and miscellaneous agents including capsaicin, cardiac glycosides, chemotherapeutic agents, cinchona alkaloids, cyclic nucleotides, cycloheximide, 2-deoxy-D-glucose, dimethylsulfoxide, insecticides, local anesthetics, poly I:poly C, spermidine and spermine, sugars, toxins and transport inhibitors. The information listed includes the species used, route of administration and dose of drug, the environmental temperature at which the experiments were performed, the number of tests, the direction and magnitude of body temperature change and remarks on the presence of special conditions such as age or lesions, or on the influence of other drugs, such as antagonists, on the response to the primary agents.

2,4-Dinitrophenol↗
PubMed1981

Arachidonate-induced hydrocephalus and hyperthermia: "dilutional tolerance" to centrally injected pyrogen and PGE1.

Conscious, unrestrained cats given multiple injections of sodium arachidonate into a lateral cerebral ventricle responded with prolonged increases in both temperature. Development of tolerance was indicated by a gradual reduction in the response to successive doses. Cross-tolerance developed to hyperthermic actions of intraventricular bacterial endotoxin and prostaglandin E1 but not to leukocytic pyrogen given IV. Tolerance to the centrally administered agents was associated with enlargement of the cerebral ventricles and was therefore at least partially due to dilution of injected solutions by the increased volume of cerebrospinal fluid. The lateral ventricles were the most affected, particularly on the side of injection. There was no indication of physical obstruction within the ventricular system. Light microscopic examination revealed regions of chronic granulomatous inflammation of the subependymal zone of the periventricular tissues. The hydrocephalus was not secondary to the large number of intraventricular injections per se, to alkalinity of the arachidonate solution or to intermittent development of hyperthermia and was apparently a specific response to arachidonate. Intraventricular administration of arachidonate provides a means of inducing hydrocephalus with minimal morbidity and mortality.

Alprostadil↗
PubMed1981

Central injection of a sigma opioid receptor agonist alters body temperature of cats.

The prototype sigma opioid receptor agonist N-allyl-normetazocine (SKF 10,047) was injected into the third cerebral ventricle of conscious, unrestrained cats, and their temperature was monitored automatically from the retroperitoneal space. In a cold environment (0 degrees C) a small, but not dose-related, hypothermia occurred after doses of 100-500 micrograms. This response was not antagonized by naloxone given intraventricularly either 15 min before or 1 hr after the opioid. A smaller hypothermia resulted after 250 micrograms SKF 10,047 when the environmental temperature was 22 degrees C, whereas hyperthermia developed in a hot environment (34 degrees C). Thus SKF 10,047 appears to allow body temperature to drift, upward in the heat and downward in the cold, a pattern indicative of thermoregulatory depression. These results are similar to those obtained in the first 2-3 hr after pentazocine administration, and they support a previous classification of the initial temperature response to centrally injected pentazocine as due to stimulation of sigma opioid receptors.

Animals↗
PubMed1981

beta-Endorphin-induced hyperthermia in the cat.

beta-Endorphin was injected into the third cerebral ventricle (ICV) of conscious, unrestrained cats. Hyperthermic response to 50 microgram of this peptide were reduced by 20-100 microgram naloxone given ICV 1 hr later. A dose of 40 microgram beta-endorphin increased body temperature at ambient temperature of 4, 22 and 34 degrees C, with the response being greater the warmer the environment. These results indicate that beta-endorphin acts on a central naloxone-sensitive receptor which is probably the v2 receptor that is activated by low doses of D-Ala2-Met-enkephalinamide to evoke a similar pattern of change in body temperature over a comparable range of ambient temperatures.

Animals↗
PubMed1980

An electromyographic method for the assessment of naloxone-induced abstinence in morphine-dependent rats.

The electromyographic (EMG) activities of suprahyoideal muscle were recorded to measure naloxone-precipitated abstinence signs in morphine-dependent rats anesthetized with urethane (1 g/kg). Rats were rendered dependent on morphine by implanting 2 morphine pellets (75 mg each) and abstinence signs were induced by intravenous injections of various doses of naloxone at different times after pellet implantation. Three precipitated abstinence signs, a) myoclonic twitch activity (MTA), b) mastication, and c) body shakes were observed on EMG recordings after the injection of naloxone. Of these symptoms, only the MTA induced by naloxone (10 microgram/kg) occurred 4h after pellet implantation and its sensitivity to naloxone increased with prolonged pellet implantation. Both mastication and precipitated shakes could be induced at 24h. However, higher doses of naloxone were required to produce the shakes than is required to induce mastication. There appears to be a positive correlation between the intensity of naloxone-induced MTA and the degree of physical dependence on morphine. Since the MTA and mastication can be induced by low doses of naloxone in morphine-dependent rats, we suggest that these two parameters may be used to detect morphine abstinence signs in this species.

Animals↗
PubMed1980

Interaction between phencyclidine (PCP) and GABA-ergic drugs: clinical implications.

Pretreatment (IP) of mice with (-) baclofen, muscimol, 4,5,6,7-tetrahydroisoxazolo (S,4-c) pyridin-3-ol hydrate (THIP), aminooxyacetic acid (AOAA) or gamma-acetylenic GABA caused a dose-dependent inhibition of thelocomotor stimulant effect of phencyclidine (PCP, 8 mg/kg). Although (-) baclofen was found to be the most effective PCP antagonist, its (+) isomer was inactive. The maximum blocking effect of AOAA was seen in animals treated 3 and 6 hr earlier. Except for gamma-acetylenic GABA, none of these drugs significantly blocked the locomotor stimulant effect of d-amphetamine (3 mg/kg, IP). Diazepam reduced d-amphetamine response, but failed to influence PCP-induced stimulation. The locomotor stimulant effect of PCP, unlike that of d-amphetamine, may be the result of a specific GABA antagonistic effect at certain dopamine-rich areas of the brain. It seems that (-) baclofen may prove to be useful in the management of PCP intoxication. Administration of higher doses of PCP (20 and 50 mg/kg) in mice pretreated with (-) baclofen resulted in the development of surgical anesthesia manifested as the loss of a) righting reflex, b) pain sensation and c) corneal reflex. The duration of the general anesthetic response was found to be a function of the doses of both (-) baclofen and PCP. The possible use of (-) baclofen as an adjuvant to general anesthetic is discussed.

Aminooxyacetic Acid↗
PubMed1980

Changes in body temperature after administration of adrenergic and serotonergic agents and related drugs including antidepressants.

This survey, the third in a series, presents extensive tabulations of literature, primarily since 1965, on thermoregulatory effects of adrenergic and serotonergic agonists and their antagonists including ergot alkaloids, amphetamines, tryptamines, monoamine oxidase inhibitors, tricyclic and other antidepressants, a variety of other agents which alter presynaptic aminergic mechanisms including reserpine, 6-hydroxydopamine, p-chlorophenylalanine, alpha-methyltyrosines, cocaine, guanethidine and bretylium. The information listed includes the species used, route of administration and dose of drug, the environmental temperature at which the experiments were performed, the number of tests, the direction and magnitude of body temperature change and remarks on the presence of special conditions, such as age or lesions, or on the influence of other drugs, such as antagonists, on the response to the primary drug.

Amphetamine↗
PubMed1980

Changes in body temperature after administration of acetylcholine, histamine, morphine, prostaglandins and related agents.

This survey, the second in a series, presents extensive tabulations of literature, primarily since 1965, on thermoregulatory effects of cholinergic agonists and antagonists, histamine and H1- and H2-receptor antagonists, narcotic analgesics and antagonists in both non-tolerant and tolerant subjects and of prostaglandins and related agents. The information listed includes the species used, route of administration and dose of drug, the environmental temperature at which the experiments were performed, the number of tests, the direction and magnitude of body temperature change and remarks on the presence of special conditions, such as age or lesions, or on the influence of other drugs, such as antagonists, on the response to the primary drug.

Acetylcholine↗
PubMed1979

Influence of opioids on central thermoregulatory mechanisms.

Of the effects of morphine and endogenous opioid peptides on thermoregulation, the one which is most likely to be of physiologic significance is hyperthermia. This increase in body temperature is the result of coordinated changes in both physiological and behavioral thermoregulatory activities and, like fever, reflects an increase in the level about which body temperature is regulated. Morphine, endogenous opioid peptides and other opioids such as pentazocine all cause hyperthermia, but the considerable variation in the dose of naloxone required to antagonize the different agonists indicates that more than one type of opiate receptor is involved in these pharmacologic responses. The minimal effect of naloxone and naltrexone on normal body temperature and on pyrogen-induced fever indicates that endogenous opioid peptides are unlikely to act physiologically via stimulation of receptors specifically sensitive to morphine. However, methionine-enkephalin is less readily antagonized by naloxone and could have a physiologic role in thermoregulation through stimulation of another type of opiate receptor.

Animals↗
PubMed1979

Changes in body temperature after administration of amino acids, peptides, dopamine, neuroleptics and related agents.

Drugs may alter body temperature by acting on any component of the thermoregulatory system. These components include heat production, heat conservation and heat loss effectors and their efferent pathways, thermosensors and their afferent pathways and neurons within the central nervous system that coordinate thermoregulatory effector activities. A thermostat is often thought to be involved although thermoregulation can be explained by models that do not incorporate a thermostat. An action on a particular component can be assessed by determining the effect of a drug on body temperature over a range of environmental temperatures and by observation and measurement of associated changes in effector activities. A scheme for such assessment is presented along with examples of its use. The study of drug-induced changes in body temperature has expanded greatly within the past decade. The primary purpose of this review is to provide a readily available source of information on interactions between certain drugs and the thermoregulatory system. Extensive tables are presented of body temperature changes after administration of amino acids, peptides, dopamine and related agents, phenothiazine neuroleptics and also phenothiazines that lack neuroleptic activity, butyrophenones, diphenylbutylpiperidines such as pimozide and miscellaneous neuroleptics. The information tabulated includes the species used, route of administration and dose of drugs, the environmental temperature at which the experiments were performed, the number of tests, the direction and magnitude of body temperature change and remarks on the presence of special conditions, such as age or lesions, or on the influence of other drugs, such as antagonists, on the response to the primary drug. Most of the cited literature was published since 1965.

Amino Acids↗
PubMed1979

Hypothermic effects of apomorphine homologues in mice.

A single intraperitoneal (i.p.) injection in mice of apomorphine (I) and its analogues norapomorphine (II), N-ethylnorapomorphine (III), N-n-propylnorapomorphine (IV) and apocodeine (V), caused dose-related decreases in deep-core body temperature. The neuroleptic agent haloperidol blocked the hypothermia produced by these apomorphines but alpha-methyl-p-tyrosine failed to do so. This indicated a direct post-synaptic stimulation of dopamine receptors. Methysergide potentiated the hypothermic effect of the apomorphine analogues. Taking the amount of apomorphine to produce a 3 degree C fall in temperature at 30 min as unity, the approximate relative potencies were: I 1.00, II 0.06, III 47.50, IV 85.00, V 0.340. The doses of the apomorphines needed to produce hypothermia were much less than those needed to cause stereotypy. The ratios of the minimal doses required to produce hypothermia, to those producing stereotypy were: I 8.82, II 4.00, III 125.00, IV 28.50, V 1.43.

Animals↗