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Biomedical subjects

B Cox

Publications and source records attributed to B Cox.

At least 217 records · Page 12Linked to original sources
PubMed1976

A comparison between amantadine and bromocriptine using the stereotyped behaviour response test (SBR) in the rat.

Amantadine (100 mg/kg), apomorphine (2.5-10 mg/kg) and bromocriptine (10-50 mg/kg) all produced stereotyped behaviour in the rat. Apomorphine was rapid in onset and of short duration, amantadine was slower to reach a maximum and bromocriptine had a delayed onset of 50 min and a prolonged action. Amantadine and bromocriptine were antagonised by pimozide (1 mg/kg for 30 min) suggesting an action on dopamine receptors, and by D,L-alpha-methyl-p-tyrosine (150 mg/kg for 3 h) suggesting an indirect action. Amantadine, though not bromocriptine, antagonised apomorphine and amantadine also reversed the SBR due to bromocriptine. Pretreatment of rats with p-chlorophenylalanine (100 mg/kg twice daily for 2 days) had no effect on bromocriptine. The significance of these results is discussed with reference to the proposed mechanism of action of bromocriptine and to the use of multiple drug therapy in Parkinsonism.

Amantadine↗
PubMed1976

Morphine hyperthermia in the rat: an action on the central thermostats.

The mechanism underlying the hyperthermic response to low doses of morphine has been investigated in rats. Doses of morphine sulfate less than 10 mg/kg i.p. caused a rise in body temperature accompanied by vasoconstriction of the cutaneous blood vessels of the tail. This hyperthermia, unlike the hypothermia following higher doses of morphine was not blocked by naloxone nor did tolerance develop to the response. Injections directly into the hypothalamus suggested that, as with the fall in temperature after high doses of morphine, the hyperthermic effect is also due to an action on the preoptic/anterior hypothalamic thermoregulatory centers. Experiments measuring thermoregulatory behavior showed that rats delayed escaping from a heat load after low doses of morphine even though their core temperature was rising. These results suggest that low doses of morphine raise the set point of the central thermostats in rats resulting in a hyperthermia mediated, at least in part, by decreased cutaneous heat loss.

Animals↗
PubMed1976

A comparison between a melanocyte-stimulating hormone inhibitory factor (MIF-I) and substances known to activate central dopamine receptors.

The tripeptide, prolyl-leucyl glycine amide, a melanocyte-stimulating hormone inhibitory factor (MIF-I), which has been reported to be effective in improving symptoms of Parkinson's disease, has been compared with drugs known to activate dopamine receptors in rat and mouse brain. Unlike apomorphine, amphetamine and amantadine it was incapable of producing sterotyped behaviour in the rat and unlike 1-dopa it was also ineffective in rats pretreated with the monoamineoxidase inhibitor mebanazine. Neither did it potentiate apomorphine nor amphetamine in this test. MIF-I did not antagonise chlorpromazine-induced loss of locomotor activity in mice, an effect which was antagonised by apomorphine, amphetamine and amantadine. Chlorpromazine hypothermia in the mouse was antagonised by 1-dopa but not by MIF-I; similar findings were obtained in reserpine-pretreated mice. These results suggest that the reported beneficial effect of MIF-I in Parkinson's disease is unlikely to be due to an interaction with dopamine systems in the brain.

Amantadine↗
PubMed1976

Dopaminergic involvement in withdrawal hypothermia and thermoregulatory behavior in morphine dependent rats.

Thermoregulatory behavior was assessed in the rat by measuring the time taken to escape from a radiant heat source. The time to excape and the rise in core temperature accompanying exposure to heat were greater in morphine dependent (1 X 75 mg SC pellet implant for 72 hr) than in control rats. Injection of naloxone (1 mg/kg) into dependent rats produced a withdrawal hypothermia and decreased the time taken to escape from the heat source. Since rats undergoing withdrawal avoided heat at the same time that their core temperature was falling, the hypothermia is most likely due to a downward setting of the central thermostats rather than a direct activation of heat loss pathways. Both the withdrawal hypothermia and the behavioral changes were blocked by pimozide pretreatment (0.5 mg/kg) implicating a dopaminergic mechanism in the downward setting of the thermostats. Administration of naloxone 144 hr after pellet implantation produced similar effects to those in the 72 hr implanted group. Injection of morphine sulfate (4 mg/kg) 144 hr after implantation increased both the core temperature and the time taken to escape from heat suggesting that the effect of morphine in the dependent rat is to produce an upward setting of the thermostats.

Animals↗
PubMed1976

Brain amines and spontaneous epileptic seizures in the Mongolian gerbil.

The seizure sensitive (WJL)UC) strain of Mongolian gerbils has been used to investigate the effects of drugs that modify central monoamine activity on spontaneous epileptiform seizures. Increasing central norepinephrine and dopamine levels significantly reduced the severity of the seizures and the importance of dopamine was further demonstrated by the protection from seizures after administration of the dopaminergic agonist apomorphine. These data indicate that a search for differences in regional levels, or turnover rates, of these amines between seizure sensitive and seizure resistant strains of gerbils might be profitable in determining the genetic deficit underlying the seizure phenomenon in these animals.

Animals↗
PubMed1976

Herpes simplex virus DNA in transformed cells: sequence complexity in five hamster cell lines and one derived hamster tumor.

Analyses of the hybridization kinetics of labeled herpes simplex virus 2 (HSV-2) DNA with DNA from five hamster cell lines transformed by UV light-irradiated HSV-2 revealed the following. (i) Viral DNA sequences were detected in all five cell lines tested. (ii) None of the cell lines contained the full complement of HSV-2 DNA. (iii) The amount of viral DNA present in the cells varied in different transformed cell lines and ranged from 8 to 32% of the HSV-2 DNA genome in 1 to 3 copies/cell. (iv) Two parallel passages of the same cell line (333-2-29) differed in the amount of viral DNA they contained. We also compared the viral DNA sequences present in (i) one transformed cell line (333-8-9) propagated serially in culture for 80 passages, (ii) a tumor produced by inoculation of a newborn hamster with the 333-8-9 cells, and (iii) a cell line derived from a hamster tumor as above and propagated in culture for 32 passages. The results show that viral DNA present in the hamster tumor and in the cells derived from the tumor had a lower sequence complexity than that present in the original serially passaged 333-8-9 cell line.

Animals↗
PubMed1976

Changes in sensitivity to apomorphine during morphine dependence and withdrawal in rats.

Stereotyped behavior induced by injection of apomorphine hydrochloride (10 mg/kg i.p) was measured in control rats, rats made dependent on morphine and dependent rats undergoing naloxone-precipitated withdrawal. The dose of apomorphine chosen was approximately the ED50 dose, so that changes in sensitivity to apomorphine in either direction could be determined. Rats which had received a subcutaneous morphine (75 mg) pellet implant 72 hours previously demonstrated an increased sensitivity to apomorphine when compared with placebo-implanted controls. During withdrawal precipitated by injection of naloxone hydrochloride (0.2 mg/kg i.p.) this increased sensitivity disappeared. Naloxone alone, in a dose of 1.0 mg/kg but not 0.2 mg/kg, significantly antagonized apomorphine-induced stereotyped behavior and these effects of apomorphine were also reduced by an acute injection of morphine sulfate (10 mg/kg). The significance of these findings with regard to changes in central dopaminergic systems during dependence and withdrawal is discussed.

Animals↗
PubMed1975

Histamine H1- and H2-receptors in the central thermoregulatory pathways of the rat.

The effects of pyrilamine and burimamide (histamine H1- and H2-receptor blockers, respectively) on the hypothermic response to histidine loading have been studied in rats. The antagonists were injected into one of three sites in the brain: the preoptic/anterior hypothalamic nuclei, the lateral ventricle, or the third ventricle. Only injections of burimamide into the third ventricle blocked the hypothermic response to systemic injection of histidine. Behavioral studies revealed that, after histidine, the animals increased their time of exposure to a heat lamp, which suggests that efferent heat loss pathways had been activated. Previous studies have shown that H1-receptor antagonists will block the hypothermic effect of histamine injected into the rostral hypothalamus. These data suggest that there are, at least, two sets of histaminergic receptors on the neuronal pathway through the hypothalamus: H1-receptors in the rostral hypothalamus and H2-receptors on neurons lying close to the wall of the third ventricle. Activation of this thermoregulatory pathway leads to increased heat loss and a fall in body temperature.

Animals↗
PubMed1975

Amantadin e tremor, a 5-hydroxytryptamine-mediated response?

Amantadine-induced tremor has been investigated using mice. Experiments with, mebanazine, reserpine, diethyldithiocarbamate, and p-chlorophenylalanine suggest that the tremorgenic action of amantadine is influenced by a balance between three putative central nervous system (CNS) transmitters: noradrenaline, dopamine and 5-hydroxytryptamine (5-HT). Drugs which reduce the concentration of the catecholamines in brain increase amantadine induced tremor. p-Chlorophenylalanine, which specifically depletes brain 5-HT, antagonises amantadine-induced tremor. An ED50 (tremor) dose of amantadine decreases the concentration of 5-hydroxy-indoleacetic acid (5-HIAA) in rat brain, particularly when this elevated due to pretreatment with 5-hydroxytryptophan. Neither inhibition of monoamine oxidase nor reduction of 5-HT-reuptake appear to be responsible for this decrease. Experiments on rat fundus suggest that amantadine increased the sensitivity of receptors to 5-HT. A similar mechanism of action in the CNS could explain both the tremor and the decrease in brain 5-HIAA. The possible relevance of these findings is discussed with respect to the known anti-Parkinson action of amantadine.

Amantadine↗
PubMed1975

The role of dopamine and noradrenaline in temperature control of normal and reserpine-pretreated mice.

Drugs with the common property of stimulating dopamine receptors, have been tested for their effects on core temperature in control and reserpine-pretreated mice. Apomorphine, amantadine, amphetamine, L-dopa and atropine all produced a fall in mouse oesophageal temperature, their efficacy correlating with their ability to activate central dopamine receptors. Amphetamine and L-dopa had a biphasic effect the initial fall being followed by a rise. In reserpine-pretreated mice only amphetamine, apomorphine, L-dopa and D.L-threo-dihydroxyphenyl-serine effectively reversed hypothermia. Amphetamine had the highest efficacy of all the drugs tested. The sum of the effects of apomorphine and D.L-threo-dihydroxyphenylserine was equivalent to the effect of amphetamine alone. It is suggested that in control mice dopaminergic mechanisms mediate the hypothermia and noradrenergic mechanisms the hyperthermia. In reserpine-pretreated mice both systems are involved in the mechanisms restoring body temperature to normal.

Amantadine↗