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T P Donohoe

Publications and source records attributed to T P Donohoe.

14 recordsLinked to original sources
PubMed1988

Infusion of the 5-hydroxytryptamine agonists RU24969 and TFMPP into the paraventricular nucleus of the hypothalamus causes hypophagia.

The 5-HT1B agonist RU24969 when given either systemically (1 mg/kg SC) or by infusion (0.5, 1.0, 2.0 micrograms) into the region of the paraventricular nucleus of the hypothalamus caused dose-dependent hypophagia in rats previously deprived of food for 18 h. Similar results were obtained at the above dosages of 1-[3-(trifluoromethyl) phenyl] piperazine (TFMPP), which acts on 5-HT1B and possibly also on 5-HT1C receptors. Neither drug significantly affected locomotion following central administration. Food intake was significantly decreased when the 5-HT1A agonist 8-OH-DPAT was given systemically (1 mg/kg SC) to rats previously deprived of food but was unaffected when 8-OH-DPAT (1 microgram) was infused into the paraventricular nucleus of both food-deprived and free feeding rats. Therefore, hypophagia occurs when hypothalamic 5-HT1B (and possibly 5-HT1C) but not 5-HT1A receptors are activated.

Animals↗
PubMed1987

Hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT is not prevented by 5-HT depletion.

The putative 5-HT1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY165163, PAPP) (1, 2, 4, 10 mg/kg s.c.) caused a significant and dose-dependent hypothermia in rats, 30 and 60 min after injection. The decreases of temperature were less marked than that caused by 8-OH-DPAT 1 mg/kg s.c.). Depletion of brain serotonin (5-HT) by 91% following pretreatment with p-chlorophenylalanine (pCPA) (150 mg/kg i.p. on three successive days) significantly enhanced the hypothermic effects of both 8-OH-DPAT (0.25 mg/kg s.c.) and LY165163 (4 mg/kg s.c.). LY165163-induced hypothermia was also somewhat enhanced following depletion of hypothalamic 5-HT by 76% after infusion of 5,7-dihydroxytryptamine (5,7-DHT) (150 micrograms) into the third ventricle. Results indicate that the hypothermia induced by the putative 5-HT1A agonists LY165163 and 8-OH-DPAT in the rat is not dependent on presynaptic 5-HT stores and is therefore probably mediated by postsynaptic 5-HT receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1987

Neurochemical and behavioural evidence for an agonist action of 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163) at central 5-HT receptors.

1-[2-(4-aminophenyl)ethyl]-4-(3-trifluoromethylphenyl)piperazine (LY 165163, PAPP) (1 mg/kg s.c.) significantly decreased 5-hydroxytryptophan (5-HTP) accumulation in cortex, hippocampus, striatum, septum, pons + medulla and midbrain and increased DOPA accumulation in the cortex and striatum following inhibition of aromatic amino acid decarboxylase with NSD 1015. LY 165163 increased food intake in non-food-deprived rats over 2, 4 and 24 h after administration. Depletion of brain 5-hydroxytryptamine (5-HT) by parachlorophenylalanine (pCPA) prevented the hyperphagic effect over 2 and 4 h after treatment with LY 165163 (1 mg/kg). Components of the postsynaptically mediated 5-HT behavioural syndrome were not detected at doses of LY 165163 between 1 and 10 mg/kg, although locomotion was increased at lower doses and the rats were inactive at the highest dose. Results in general indicate that LY 165163 is a centrally active agonist at 5-HT presynaptic receptors.

5-Hydroxytryptophan↗
PubMed1987

Immobilisation stress-induced anorexia is not due to gastric ulceration.

The relationship between the anorexia following immobilisation and the associated gastric pathology in male and female rats was investigated. Male rats were injected with saline or the histamine-H2. antagonist, ranitidine, which inhibits gastric acid secretion but does not readily enter the brain. Thirty minutes later, the animals were immobilised for 2 hours. Ranitidine pretreatment reduced the number of gastric lesions but had no effect on the degree of stress-induced anorexia. The number of gastric lesions did not correlate significantly with the degree of anorexia or weight loss. Previous studies have reported that female rats (unlike males) exhibit anorexia after repeated daily immobilisations and have greater gastric pathology following stress. Therefore, in a second experiment, female rats were pretreated with saline or ranitidine and immobilised for 2 hours/day for 4 days. The drug did not decrease the number of lesions observed after this treatment. However, as in the first experiment, the number of lesions did not correlate significantly with anorexia or weight loss. It is therefore unlikely that immobilisation stress-induced anorexia in either male or female rats is merely a consequence of gastric ulceration.

Animals↗
PubMed1987

The influence of cyproheptadine on immobilization and oestradiol benzoate induced anorexia in ovariectomized rats.

Repeated bodily immobilization significantly reduced the food intake of ovariectomized rats. Additionally, immobilization and oestradiol benzoate were found to produce additive effects in depressing feeding. To determine whether serotonergic mechanisms are involved in the stress- and oestrogen-induced anorexia, the 5-HT antagonist cyproheptadine was given to ovariectomized rats that were immobilized and treated with oestradiol benzoate. Cyproheptadine had no effect on the anorexia produced by oestradiol. The food intake of immobilized rats treated with cyproheptadine was similar to control values, suggesting 5-HT involvement in the stress-induced anorexia. However, cyproheptadine had no ameliorating effects on the changes in body weight following immobilization treatment. The implications of these findings are discussed in relation to a possible neuroendocrine basis for anorexia.

Animals↗
PubMed1987

Blockade of dopamine receptors explains the lack of 5-HT stereotypy on treatment with the putative 5-HT1A agonist LY165163.

The putative serotonin (5-HT)1A agonist 1-[2-(4-aminophenyl)ethyl]-4-(3-trifluormethylphenyl) piperazine (LY165163, PAPP) induces hyperphagia and hypothermia in rats, but unlike other 5-HT agonists, does not induce 5-HT stereotypy even at high doses (10 mg/kg sc). LY165163 (1 mg/kg) increased striatal DOPA accumulation in animals treated with the aromatic amino acid decarboxylase inhibitor 3-hydroxy-benzylhydrazine (NSD 1015) (100 mg/kg ip). This increase was also found when the drug was given to animals pretreated with parachlorophenylalanine (pCPA) (150 mg/kg ip daily for 3 days). LY165163 (2 and 4 mg/kg sc) inhibited stereotyped behaviour induced by the dopamine (DA) agonist apomorphine (2 mg/kg sc). LY165163 (2, 4, 10 mg/kg sc) also inhibited stereotyped components of the 5-HT syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT; 5 mg/kg ip) which previous studies (e.g. Andrews et al. 1982) suggested to require DA (head weaving, reciprocal forepaw treading). Thus, while other 5-HT1A agonists such as 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) cause stereotypy, this does not occur with LY165163, probably because the drug blocks DA receptors.

Animals↗
PubMed1984

Stress-induced anorexia: implications for anorexia nervosa.

Recent studies have suggested that stress may be a precipitating factor in the etiology of anorexia nervosa. The present paper examines the possible mechanisms involved in stress-induced anorexia and suggests how stress-induced changes in opiate systems, the hypothalamic-pituitary-adrenal axis and serotonergic systems may provide an explanation of many of the physiological and behavioral responses observed in anorexia nervosa. The present paper suggests that certain psychosocial and endocrinological factors may interact to provide the setting conditions for the syndrome. Finally, it is suggested that a dual therapeutic approach is required in that the syndrome needs to be treated both physiologically and psychologically to prevent relapse.

Adolescent↗
PubMed1984

Effects of stereoisomers of estradiol on food intake, body weight and hoarding behavior in female rats.

The effects of 17-alpha and 17-beta estradiol on food intake, body weight and hoarding behavior in ovariectomised rats were investigated. For five days, ten animals received subcutaneous injections of both isomers (10 micrograms/kg/day) in a counterbalanced design. Hoarding tests were conducted on the last three days of each 5-day injection period. 17-Alpha estradiol significantly reduced food intake but was without effect on body weight. 17-Beta estradiol reduced food intake significantly more than the alpha form and also significantly reduced body weight. These differential effects suggest that stereoisomers of estradiol may be acting on separate regulatory systems. The treatments did not change hoarding activity compared to pre-treatment levels.

Animals↗
PubMed1983

Effects of ovariectomy, estrogen treatment and CI-628 on food intake and body weight in female rats treated neonatally with gonadal hormones.

Body weights and skeletal growth of female rats treated neonatally with low doses of testosterone propionate (TP) or estradiol benzoate (FB) were greater than oil-treated controls. After ovariectomy at 75 days of age EB-treated animals gained less weight than did the oil-treated controls and TP-treated rats which were comparable in weight gain. Neonatal treatment with TP or EB produced decreased sensitivity to the anorexic and weight-limiting effects of estrogen treatment after ovariectomy. However, all groups were equally sensitive to the anorexic effects of a single dose of CI-628. The possible mechanisms by which neonatal treatments with gonadal hormones influence food intake and body weight regulation are discussed.

Animals↗
PubMed1982

Modulation of food intake by hypothalamic implants of estradiol benzoate, estrone, estriol and CI-628 in female rats.

ovariectomised rats were implanted unilaterally with cannulae aimed at the ventromedial nucleus-arcuate region of the hypothalamus. Crystalline implants of estradiol benzoate and of the antiestrogenic compound CI-628 over a 72-hour stimulation period caused significantly greater food intake reductions than did implants of cholesterol. More dorsal and lateral placements were generally ineffective in reducing food intake. Implants of estrone and estriol produced equivalent reductions in food intake and body weight to those produced by estradiol benzoate. The possible molecular mode of action is discussed.

Animals↗