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B Cox

Publications and source records attributed to B Cox.

At least 163 records · Page 9Linked to original sources
PubMed1982

Possible mechanism of 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in DRN lesioned rats.

5-Methoxy-N,N-dimethyltryptamine (5-MeODMT) (7.5 mg/kg SC) caused a contralateral turning in rats with a unilateral lesion of the dorsal raphe nucleus (DRN). This turning behaviour was blocked by pretreatment with putative 5-HT antagonists, methysergide, cyproheptadine and cinanserin. The peripheral 5-HT antagonist, xylamidine, also prevented the response to 5-MeODMT. Of the other neurotransmitter antagonists, only haloperidol was active, hyoscine, picrotoxin, naloxone and strychnine were ineffective. Pretreatment with alpha-methyl-p-tyrosine (alpha-MT) also significantly reduced the turning response to 5-MeODMT. These results indicate that a central dopaminergic system is involved in 5-MeODMT-induced turning behaviour. This suggestion is supported by the finding that an ipsilateral turning in response to 5-MeODMT was observed in the rats with additional 6-hydroxydopamine (6-OHDA) lesions of the medial forebrain bundle (MFB). The possible mechanisms by which 5-MeODMT induced turning in DRN lesioned rats are discussed.

Animals↗
PubMed1982

Characterization of 5-hydroxytryptaminergic autoreceptors in the rat hypothalamus.

5-hydroxytryptamine (5-HT) (3 X 10(-9) to 10(-6) M) produced a concentration-related inhibition of potassium-evoked tritium release from slices of rat hypothalamus preloaded with [3H]-5-HT. The response to 5-HT was unaffected by the presence of yohimbine (10(-6) M), pimozide (10(-7) M), domperidone (10(-7) M) or tetrodotoxin (10(-7) M), indicating that the response was not mediated via alpha 1- or alpha 2-adrenoceptors or dopamine receptors and that the receptors that were involved were located directly on the 5-HT nerve terminal. The 5-HT antagonist metergoline (10(-8) to 3 X 10(-7) M) produced a parallel rightward shift in the concentration-effect curve to 5-HT with no reduction in the size of the maximum response. The pA10 value for metergoline was 6.82 and the slope of the Arunlakshana-Schild plot was not significantly different from 1.0 indicating that it was a competitive antagonist. Methiothepin produced a similar effect to metergoline whilst cyproheptadine and methysergide were less potent as antagonists of 5-HT and were not competitive. Cinanserin was inactive. Thus we have characterized the 5-HT autoreceptor in the rat hypothalamus using a classical pharmacological approach and found that it has more in common with the autoreceptor which we have previously identified in the raphe nuclei of the rat than it has with the 5-HT receptor located on dopamine neuroterminals in the striatum.

5-Methoxytryptamine↗
PubMed1981

Supersensitivity of nigral serotonin receptors and rat rotational behaviour.

Direct injections of 5-hydroxytryptamine (5-HT) into the corpus striatum (CS) and substantia nigra (SN) after unilateral 5,7-dihydroxytryptamine (5,7-DHT) of the dorsal raphe nucleus (DRN), resulted in a significant dose related contralateral turning behaviour in SN-injected but not in CS-injected animals. Receptor binding studies in these animals revealed a 3 fold increase in [3H]5-HT binding sites (Bmax) and a similar increase in affinity constant (KD) in the SN from the lesioned side when compared with the unlesioned side. There was no change in binding characteristics in the CS of DRN-lesioned animals. The data presented would confirm our previous findings that nigral 5-HT receptors become supersensitive after denervation of the DRN-SN pathway.

Animals↗
PubMed1981

GABA enhancement of [3H]dopamine release from slices of rat striatum: dependence on slice size.

The effect of GABA on potassium-evoked tritium release from two sizes of ribbon of rat striatum previously loaded with [3H]dopamine was studied. GABA had no effect on the release of tritium from 100 x 100 mum ribbons but produced a dose-related enhancement of potassium-evoked tritium release from 250 x 250 mum ribbons. The enhancement was unaffected by the presence of bicuculline or picrotoxin but was antagonised by tetrodotoxin. The effect of GABA was not mimicked by the GABA agonists muscimol or baclofen. The possible involvement of an interneurone is discussed. From antagonist studies the neurotransmitter released by the postulated interneurone did not appear to be acetylcholine, 5-hydroxytryptamine, glycine, glutamate or enkephalin.

Animals↗
PubMed1981

5-Hydroxytryptamine-induced hypothermia in rats as an in vivo model for the quantitative study of 5-hydroxytryptamine receptors.

Intrahypothalamic injection of 5-hydroxytryptamine (5-HT) caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 degrees C. The hypothermia was blocked by 5-HT antagonists with a relative potency of methiothepin greater than methergoline greater than methysergide greater than cinanserin greater than cyproheptadine. The peripheral 5-HT antagonist, xylamidine, was not an antagonist, suggesting the hypothermia was of central origin. Other neurotransmitter antagonists, haloperidol, atropine, phentolamine, and propranolol failed to prevent 5-HT-induced hypothermia. This suggests that the hypothermic response to 5-HT can be used for a quantitative study of drug action at central 5-HT receptors.

Animals↗
PubMed1981

Characterisation of inhibitory 5-hydroxytryptamine receptors that modulate dopamine release in the striatum.

The effect of a series of indoleamines on the potassium-evoked tritium release of previously accumulated [3H]dopamine from rat striatal slices has been investigated. The indoleamines 5-hydroxytryptamine, 5-methoxytryptamine, 5-methoxy-N,N'-dimethyltryptamine and tryptamine (10(-7) to 10(-5) M) all reduced potassium-evoked release of tritium, to a maximum of 50%. The uptake of [3H]dopamine was unaffected by these compounds. A series of 5-hydroxytryptamine antagonists were examined for their ability to reduce the inhibition of potassium-evoked tritium release induced by 5-methoxytryptamine. The relative order of antagonist potency obtained was methysergide greater than metergoline greater than methiothepin greater than cinanserin greater than cyproheptadine greater than mianserin, and was consistent with an action on 5-hydroxytryptamine receptors. It is concluded that there are inhibitory 5-hydroxytryptamine receptors located on the terminals of dopaminergic neurones in the striatum.

Animals↗
PubMed1981

Different hypothalamic receptors mediate 5-hydroxytryptamine- and tryptamine-induced core temperature changes in the rat.

1 Unilateral intrahypothalamic injection of 5-hydroxytryptamine (5-HT) caused a dose-related fall in core temperature in rats, whereas injection of tryptamine into the same site caused a dose-related rise in core temperature. 2 The core temperature changes induced by 5-HT or tryptamine were inhibited by intrahypothalamic pretreatment with indoleamine receptor antagonists in a dose-related manner. 3 Other neurotransmitter antagonists, haloperidol, atropine, phentolamine and (-)-propranolol, had no significant effect on core temperature changes induced by 5-HT or tryptamine. 4 A differential antagonism was observed for the indoleamine receptor antagonists against 5-HT and tryptamine-induced core temperature changes. Methergoline and triflupromazine were more selective against tryptamine-induced hyperthermia, while cyproheptadine was more selective against 5-HT-induced hypothermia. 5 Intrahypothalamic pretreatment with 5,-7-dihydroxytryptamine (5,7-DHT) 42 nmol in 2 microliter inhibited tryptamine-induced hyperthermia, but was without effect on 5-HT-induced hypothermia. 6 These results suggest the possible existence of two different receptor populations within the preoptic anterior hypothalamus in rats; one specific for 5-HT and the other for tryptamine.

5,7-Dihydroxytryptamine↗
PubMed1981

Postreplication repair in Saccharomyces cerevisiae.

Postreplication events in logarithmically growing excision-defective mutants of Saccharomyces cerevisiae were examined after low doses of ultraviolet light (2 to 4 J/m2). Pulse-labeled deoxyribonucleic acid had interruptions, and when the cells were "chased," the interruptions were no longer detected. Since the loss of interruptions was not associated with an exchange of pyrimidine dimers at a detection level of 10 to 20% of the induced dimers, we concluded that postreplication repair in excision-defective mutants (or leaky mutants) does not involve molecular recombination. Pyrimidine dimers were assayed by utilizing the ultraviolet-endonuclease activity in extracts of Micrococcus luteus and newly developed alkaline sucrose gradient techniques, which yielded chromosomal-size deoxyribonucleic acid after treatment of irradiated cells.

DNA Repair↗
PubMed1980

Mercapto steroids in protection against mercury and lead poisoning.

When thiocholesterol is administered as liposomes, it provides significant protection against methylmercuric chloride in mice when given in three intraperitoneal injections, 0.5 hr before and 2 and 8 hr after the methylmercuric chloride. Thiositosterol, 5 alpha-cholestane-2 beta, 3 alpha-dithiol, and 5 beta-cholane-3 beta, 24-dithiol also are active, but 3 alpha-mercapto-5 alpha-pregnan-20-one, 6 beta-mercapto-5 alpha-cholestane-3 beta, 5 alpha-diol, 3 beta-mercapto-5 beta-cholanic acid, and adamantanethiol are ineffective under these conditions. Adamantanethiol is somewhat effective when administered in soybean oil. Cholestanyl amine was treated with acetylthiosuccinic anhydride to give the half amide; cleavage with hydroxylamine liberated the thiol group. This product is active against both methylmercuric chloride and lead nitrate.

Animals↗
PubMed1980

Mechanism of action of dopamine on the guinea-pig gastro-oesophageal junction in vitro.

1 The effect of dopamine on longitudinal muscle strips of the guinea-pig isolated gastro-oesophageal junction was compared with the response obtained to phenylephrine, isoprenaline and clonidine. Phenylephrine (5 x 10(-7) to 5 x 10(-5) M) produced a dose-related contraction, whilst dopamine (10(-6) to 10(-4) M) and isoprenaline (5 x 10(-7) to 2 x 10(-5) M) produced dose-related relaxations. Clonidine was ineffective in doses up to 10(-5) M. 5-Hydroxytryptamine (5-HT) produced a contraction. 2 Phenylephrine was antagonized by alpha 1-adrenoceptor antagonists but unaffected by beta-adrenoceptor antagonists, whilst the opposite was the case for isoprenaline. A mixture of alpha- and beta-adrenoceptor antagonists was required to inhibit completely dopamine-induced relaxations. 5-HT (3 x 10(-7) M) was specifically antagonized by methysergide (3 x 10(-6) M). 3 pA2 values for a range of alpha-adrenoceptor and dopamine receptor antagonists were determined against dopamine and phenylephrine. The relative order of potency of the antagonists was the same for both antagonists and was prazosin greater than spiroperidol greater than phentolamine greater than domperidone greater than haloperidol, with pimozide and metoclopramide being inactive. 4 Tyramine caused dose-related relaxations of the gastro-oesophageal strips which were susceptible to the same range of antagonists as dopamine. 5 Cocaine (6 x 10(-6) M) and desmethylimipramine (3 x 10(-7) M) reduced the relaxations induced by dopamine and tyramine but there were quantitative differences in the antagonism. 6 Tissue from reserpine pretreated guinea-pigs was insensitive to tyramine but the response to dopamine was only partly reduced. 7 Histological examination of the strips revealed the presence of smooth muscle but only a sparse adrenergic innervation. 8 The results suggest that dopamine acts partly indirectly and partly directly on postjunctional alpha- and beta-adrenoceptors. There is no evidence for an action on specific dopamine receptors.

Animals↗
PubMed1980

Further evidence for a physiological role for hypothalamic dopamine in thermoregulation in the rat.

1. Intrahypothalamic injection of either dopamine or noradrenaline in a dose volume of 1 mul. caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degrees C.2. The hypothermic effects of dopamine (10 mug) and noradrenaline (2 mug) were selectively antagonized by systemic pre-treatment with pimozide (0.5 mg/kg) and phentolamine (1 mg/kg) respectively.3. The location of the dopamine- and noradrenaline-sensitive sites were defined more accurately by reducing the dose volume to 0.5 mul. and making injections at different points throughout the preoptic region.4. Both the dopamine- and the noradrenaline-sensitive sites were located within the preoptic region, but they did not have identical locations being separated by a distance of 0.4 mm.5. Unilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.) caused a significant fall in core temperature, which was antagonized by systemic injection of either pimozide or phentolamine.6. Rats placed 0.65 m below a 250 W infra-red lamp responded to the imposed heat load by vasodilation of tail skin blood vessels, indicated by an increased tail skin temperature.7. Rats were tested two weeks after bilateral intrahypothalamic injection of 6-hydroxydopamine (10 mug in 2 mul.). This pre-treatment significantly reduced the increase in tail skin temperature so that the rats were less able to withstand the imposed heat load. Rats receiving similar 6-hydroxydopamine pre-treatment following injection of desipramine (25 mg/kg, I.P.) were also less able to cope with a heat load.8. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the dopamine-sensitive site.9. Pre-treatment with 6-hydroxydopamine reduced both the dopamine and the noradrenaline concentration in the dopamine-sensitive site. Pre-treatment with desipramine and 6-hydroxydopamine selectively reduced dopamine.10. These results indicate that there are receptors for both dopamine and noradrenaline in the preoptic anterior hypothalamus, which mediate a fall in core temperature in rats, but the evidence suggests that it is endogenous dopamine which is more likely to play an important physiological role.

Animals↗
PubMed1980

A dopamine-5-hydroxytryptamine link in the hypothalamic pathways which mediate heat loss in the rat.

1. Intrahypothalamic injection of either dopamine or 5-hydroxytryptamine (5-HT) in a dose volume of 1 microliters caused a fall in core temperature in lightly restrained rats maintained at an ambient temperature of 17 +/- 1 degree C. 2. Haloperidol (6.5 n-mole), a dopamine antagonist, prevented the hypothermic effect of dopamine (65 n-mole), but was ineffective against the response to either intrahypothalamic 5-HT (114 n-mole) or oxotremorine (6.0 n-mole). 3. Methysergide (14 n-mole) and cryproheptadine (17 n-mole) blocked the effect of both 5-HT and dopamine. However, these same doses failed to antagonise the effect of oxotremorine. 4. Rats placed on 0.65 m below a 250 W infra-red lamp responded to the imposed heat load vasodilation of tail skin blood vessels, as indicated by an increased tail skin temperature. 5. Rats tested 2 weeks after bilateral intrahypothalamic injection of 5,6-dihydroxytryptamine (42 n-mole in 2 microliters) showed a significant reduction in their tail skin temperature response and were less able to withstand the imposed heat load. 6. Three serial sections (0.8 mm thick) were prepared from the preoptic area of the rat brain, one anterior, one posterior and one corresponding to the previously defined dopamine-sensitive site. 7. Pretreatment with 5,6-dihydroxytryptamine significantly reduced the 5-HT concentration in the dopamine sensitive site, but had no effect on the concentration of dopamine. This pretreatment blocked dopamine but not 5-HT-induced hypothermia. 8. The 5-hydroxyindoleacetic acid (5HIAA) concentration in the hypothalamus of the normal rat exposed to a heat load was found to be significantly elevated, whereas there was no change in the 5HIAA concentration in the cortex. 9. Slices of rat preoptic hypothalamus and hippocampus were incubated with [3H]5-HT (0.2-2 microM). These slices accumulated 5-HT with properties characteristic of a neuronal uptake process. 10. Perfusion with either dopamine (greater than 50 microM) or apomorphine (greater than 200 microM) enhanced the release of [3H]5-HT from the prelabelled hypothalamic slices, but failed to stimulate release from hippocampal slices. 11. The release of [3H]5-HT from preoptic slices by dopamine and apomorphine was antagonised by the dopamine antagonists haloperidol (2 microM) and (+) isomer of butaclamol (1 microM), the (-) isomer of butaclamol was inactive. 12. These results support the hypothesis of a dopamine-5HT link in the hypothalamic thermoregulatory pathways of the rat.

Animals↗