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T Sharp

Publications and source records attributed to T Sharp.

At least 19 recordsLinked to original sources
PubMed1992

Selective 5-HT1A and 5-HT2 receptor-mediated adrenocorticotropin release in the rat: effect of repeated antidepressant treatments.

The 5-HT receptor agonists, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) produced dose-dependent increases in plasma adrenocorticotropin (ACTH) in the male rat by activation of 5-HT1A and 5-HT2 receptors respectively. The ACTH response to DOI was enhanced by repeated administration of electroconvulsive shock (five over 10 days) but abolished by the tricyclic antidepressant, amitriptyline (20 mg/kg for 14 days). In contrast 21 days lithium treatment failed to alter DOI-induced ACTH release. Neither repeated electroconvulsive shock, nor amitriptyline, nor lithium altered the ACTH response to 8-OH-DPAT. These data are consistent with results from ligand binding and behavioural studies which suggest that the sensitivity of brain 5-HT2 receptors is increased by repeated electroconvulsive shock but attenuated by tricyclic antidepressant treatment. In contrast, our data suggest that the antidepressant treatments studied do not alter the sensitivity of the 5-HT1A receptors involved in ACTH release.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

Effect of naloxone-precipitated morphine withdrawal on noradrenaline release in rat hippocampus in vivo.

Here we investigated the effect of naloxone-precipitated morphine withdrawal on the release of noradrenaline in hippocampus of the anaesthetised rat. Naloxone (1 mg/kg i.p.) injected 3 and 24 h, but not 3 weeks, after eight daily injections of morphine, induced an immediate increase in hippocampal noradrenaline release. This striking effect of naloxone was markedly attenuated by pretreatment with clonidine (0.1 mg/kg s.c.). These findings provide direct evidence for a marked release of noradrenaline in hippocampus during opiate withdrawal in vivo.

Animals↗
PubMed1992

Clonidine but not nifedipine prevents the release of noradrenaline during naloxone-precipitated opiate withdrawal: an in vivo microdialysis study in the rat.

In this study we have examined whether the alpha 2-adrenoceptor agonist clonidine and the calcium channel antagonist nifedipine firstly inhibit the naloxone-precipitated withdrawal syndrome in morphine-dependent rats and secondly reduce central noradrenaline release during withdrawal. We demonstrate that both clonidine (0.1 mg/kg) and nifedipine (10 mg/kg) attenuate the naloxone-precipitated withdrawal syndrome. Using in vivo microdialysis, we demonstrate that following naloxone the release of noradrenaline, as measured by perfusates from hippocampus, increases 300% in morphine-dependent rats. However, whilst pretreatment with clonidine inhibited this increased noradrenaline release, nifedipine did not. These findings suggest that whilst the action of clonidine in attenuating the morphine withdrawal syndrome may be mediated by decreasing central noradrenaline release, this is not the mechanism by which nifedipine acts.

Animals↗
PubMed1992

Evidence that the large neutral amino acid L-valine decreases electrically-evoked release of 5-HT in rat hippocampus in vivo.

L-Valine competes with tryptophan for transport into the brain and has previously been shown to decrease brain 5-HT synthesis. In the present study, the effect of L-valine on electrically evoked hippocampal 5-HT release was determined in the anaesthetized rat using microdialysis. In control animals two electrical stimulations of the dorsal raphe nucleus 120 min apart (S1 and S2, respectively) released similar amounts of 5-HT. In contrast, in animals which received L-valine (200 mg/kg) between stimulations, S2 released a significantly smaller amount of 5-HT than did S1, although basal 5-HT release was unchanged. The data demonstrate that L-valine decreases the electrically-evoked release of 5-HT in hippocampus in vivo.

Animals↗
PubMed1992

Effects of the 5-HT1A partial agonists gepirone, ipsapirone and buspirone on local cerebral glucose utilization in the conscious rat.

The azospirones gepirone (10 mg/kg), ipsapirone (10 mg/kg) and buspirone (10 mg/kg) were examined for their effect on regional cerebral glucose utilization in conscious rats using quantitative 2-deoxy-glucose autoradiography. All three 5-HT1A partial agonists reduced glucose utilization in the hippocampus and dentate gyrus by 20-25% and increased glucose utilization by 38-65% in the lateral habenular nucleus; an important relay between striatal/limbic areas and the mid-brain raphe nuclei. The findings emphasize the potential importance of the hippocampus as a site of action for 5-HT1A receptor active drugs in vivo and also suggest that functional activity in the striatal/limbic-habenular-raphe pathway may be influenced by gepirone, ipsapirone and buspirone.

Animals↗
PubMed1992

Effect of acute administration of L-tryptophan on the release of 5-HT in rat hippocampus in relation to serotoninergic neuronal activity: an in vivo microdialysis study.

Here we have used the brain microdialysis method to test the effect of the 5-HT precursor L-tryptophan on 5-HT release. The release of endogenous 5-HT was measured in ventral hippocampus of the anesthetized rat both under basal conditions and when serotoninergic neuronal activity was raised by electrical stimulation of the dorsal raphe nucleus (DRN). Low frequency electrical stimulation of the DRN evoked a frequency-dependent (2-10 Hz) release of hippocampal 5-HT. The electrically evoked release of 5-HT was markedly enhanced by pretreatment with L-tryptophan (50 and 100 mg/kg i.p.). The effect of L-tryptophan on evoked release of 5-HT was dose-related, detectable at low (2 Hz) stimulation frequencies, and became stronger as the stimulation frequency increased. L-Tryptophan (10, 50 and 100 mg/kg i.p.) had no effect on basal output of 5-HT. We conclude from these findings that elevation of 5-HT precursor availability increases 5-HT release in hippocampus in vivo under conditions of increased serotoninergic neuronal activity.

Animals↗
PubMed1992

Effect of 5-hydroxy-L-tryptophan on the release of 5-HT in rat hypothalamus in vivo as measured by microdialysis.

The effect of systemic administration of the 5-HT precursor, 5-hydroxy-L-tryptophan (5-HTP) on the release of 5-HT in the lateral hypothalamus of the chloral hydrate-anaesthetized rat in vivo was examined using brain microdialysis. Administration of 5-HTP caused an immediate increase of 5-HT in dialysates, which was long lasting (greater than or equal to 140 min) and dose-dependent (30-100 mg/kg i.p.). When calcium was omitted from the perfusion medium, thereby limiting exocytosis, levels of basal 5-HT were significantly decreased and the 5-HTP-induced response of 5-HT was markedly attenuated. Administration of the 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (0.25 mg/kg i.p.), which selectively inhibits serotoninergic neuronal activity by activation of the somatodendritic 5-HT autoreceptor, significantly decreased basal levels of 5-HT and markedly attenuated the 5-HTP-induced increase in 5-HT. The data demonstrate that systemic administration of 5-HTP caused an increase in the release of 5-HT in the hypothalamus. Furthermore, this release occurred by a calcium-dependent mechanism (probably exocytosis), was dependent on serotoninergic neuronal activity and predominantly derived from 5-HT neurones. The findings are discussed in relation to the behavioral and neuroendocrine effects of increasing availability of the 5-HT precursor.

5-Hydroxytryptophan↗
PubMed1992

The putative 5-HT1A antagonist BMY 7378 blocks 8-OH-DPAT-induced changes in local cerebral glucose utilization in the conscious rat.

It has previously been shown that the 5-HT1A agonist, 8-OH-DPAT, caused discrete changes in cerebral glucose utilization in the rat, as assessed by quantitative 2-deoxyglucose autoradiography. Here, the effect of the putative 5-HT1A antagonist, BMY 7378, on regional cerebral glucose utilization was examined, when injected alone and in rats treated with 8-OH-DPAT. In control rats, BMY 7378 (5 mg/kg, s.c.) markedly increased glucose utilization in the lateral habenular nucleus and moderately reduced glucose utilization in the hippocampal formation. Pretreatment with BMY 7378 (5 mg/kg) significantly attenuated the reductions in glucose utilization in the hippocampus, entorhinal, piriform and cingulate cortex, induced by 8-OH-DPAT (0.25 mg/kg). The 8-OH-DPAT-induced increase in glucose utilization in the copula pyramis, that is putatively associated with the appearance of the 5-HT behavioural syndrome, was also blocked by BMY 7378, as was the behavioural syndrome. In summary, BMY 7378 produced few of the discrete changes in cerebral glucose utilization that are seen with 8-OH-DPAT. However, many of the changes induced by 8-OH-DPAT were reversed by BMY 7378. These data are consistent with the hypothesis that the effects of 8-OH-DPAT on regional cerebral glucose utilization are mediated by 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1992

The role of breakfast in the treatment of obesity: a randomized clinical trial.

Fifty-two moderately obese adult women were stratified according to their baseline breakfast-eating habits and randomly assigned a weight-loss program. The no-breakfast group ate two meals per day and the breakfast group ate three meals per day. The energy content of the two weight-loss programs was identical. After the 12-wk treatment, baseline breakfast eaters lost 8.9 kg in the no-breakfast treatment and 6.2 kg in the breakfast treatment. Baseline breakfast skippers lost 7.7 kg in the breakfast treatment and 6.0 kg in the no-breakfast treatment. This treatment-by-strata-by-time interaction effect (P less than 0.06) suggests that those who had to make the most substantial changes in eating habits to comply with the program achieved better results. Analyses of behavioral data suggested that eating breakfast helped reduce dietary fat and minimize impulsive snacking and therefore may be an important part of a weight-reduction program.

Adolescent↗
PubMed1992

Evidence that 5-HT2 receptor activation decreases noradrenaline release in rat hippocampus in vivo.

1. Recent electrophysiological studies have shown that 5-HT2/5-HT1C receptor agonists inhibit the electrical activity of noradrenergic neurones in the rat locus coeruleus. Here we examine the effect of various agonists and antagonists of 5-HT2/5-HT1C receptors on noradrenaline release in hippocampus of anaesthetized rats using microdialysis. 2. Subcutaneous administration of the 5-HT2/5-HT1C receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI: 0.2 and 0.5 mg kg-1), caused a marked decrease (50% of pre-drug levels 60 min after injection) of noradrenaline in hippocampal dialysates which was long-lasting (greater than 120 min). Noradrenaline output also decreased in response to administration of the structural analogue of DOI, 1-(2,5-dimethoxy-4-bromophenyl)-2-aminopropane (DOB: 1 mg kg-1, s.c.). 3. The effect of DOI on noradrenaline output was prevented by pretreatment with the 5-HT2/5-HT1C receptor antagonist, ritanserin (0.4 mg kg-1, s.c.). Spiperone (0.2 and 1 mg kg-1, s.c.), a 5-HT2/dopamine D2 receptor antagonist which has low affinity for 5-HT1C receptors, also antagonized the effect of DOI (0.5 mg kg-1, s.c.). Sulpiride (50 mg kg-1, s.c.), a dopamine D2 receptor antagonist did not alter the response to DOI (0.5 mg kg-1, s.c.). 4. Both the non-selective 5-HT receptor agonist, quipazine (1 mg kg-1, s.c.), and the 5-HT-releasing agent, p-chloroamphetamine (2 mg kg-1, s.c.), decreased noradrenaline release in hippocampus and these effects were antagonized by pretreatment with ritanserin (0.4 mg kg-1, s.c.).5. Our data suggest that in vivo, noradrenaline release in hippocampus is inhibited by 5-HT2 receptor activation. This effect is probably associated with a decrease in noradrenergic neuronal activity.

DOM 2,5-Dimethoxy-4-Methylamphetamine↗
PubMed1992

The effects of aerobic exercise on psychological adjustment: a randomized study of sedentary obese women attempting weight loss.

This study evaluated the psychological effects of aerobic conditioning in 40 moderately obese, sedentary women participating in a 12-week behavioral weight loss program. Participants were randomly assigned to a no-exercise or moderate walking condition. Emotional impact of the treatment was assessed in two ways: (1) Subjects reported subjective mood prior to each eating episode and (2) the SCL-90-R was administered before and after the program. Exercisers lost more weight and body fat than non-exercisers. Both groups of subjects showed numerous improvements in mood as a result of participating in the weight loss program. Exercise had no specific differential effect on emotions as measured by daily mood ratings or the SCL-90-R. Exercise did not appear to add appreciably to the psychological benefits of losing weight in this sedentary obese population. Future studies utilizing longer periods of aerobic exercise training, larger sample size, and exercise specific measures are recommended.

Adaptation, Psychological↗
PubMed1991

Release of 5-hydroxytryptamine (5-HT) from medullary and mesencephalic raphé neurones after grafting to the rat hippocampus: evidence for regulation by 5-HT1A autoreceptors.

The overflow and metabolism of serotonin (5-HT) from transplants of embryonic medullary and mesencephalic raphé neurones in the previously 5-HT-denervated hippocampus have been analyzed in vivo using microdialysis. Output of 5-HT and its metabolite 5-hydroxyindolacetic acid (5-HIAA) from such grafts was as great (medullary) or greater (mesencephalic) than that measured in the normal intact hippocampus. Systemic administration of the putative 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) led to a 50-80% reduction in 5-HT levels in hippocampal dialysates from both intact and raphé grafted hippocampus. Since 8-OH-DPAT normally reduces 5-HT release from the nerve terminal via activation at the somatodendritic 5-HT1A autoreceptor and subsequent inhibition of impulse flow, the results indicate that 5-HT output from both medullary and mesencephalic raphé grafts can be regulated by autoreceptors and is dependent on serotoninergic neuronal activity.

5,7-Dihydroxytryptamine↗
PubMed1991

Effect of the 5-HT1A receptor agonist 8-OH-DPAT on the release of 5-HT in dorsal and median raphe-innervated rat brain regions as measured by in vivo microdialysis.

Recent electrophysiological studies, measurements of 5-HT synthesis and in vivo voltammetry recordings of 5-HT metabolism have suggested that serotoninergic neurones in the median raphe (MR) are less sensitive to 5-HT1A autoreceptor stimulation relative to those in the dorsal raphe (DR). To further study the putative differences in regulation between ascending 5-HT projections from the raphe nuclei we have used microdialysis to measure the release of 5-HT in ventral hippocampus, globus pallidus, dorsal hippocampus, frontal cortex, nucleus accumbens and medial septum, following systemic administration of the specific 5-HT1A agonist 8-OH-DPAT. The results show that the baseline output of 5-HT was similar in each of the areas studied. While 8-OH-DPAT decreased dialysate levels of 5-HT in all areas, the inhibition of 5-HT release seen in globus pallidus was significantly less marked compared to that observed in the other five regions. The results indicate that 5-HT1A autoreceptor-mediated control of 5-HT release is functional in all of the brain areas studied, including those receiving a preferential 5-HT innervation from the DR and MR. We find little evidence in support of the idea that brain 5-HT neuronal projections are heterogenous with respect to 5-HT1A autoreceptor regulation of 5-HT release; the globus pallidus, however representing a possible exception to this.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1991

Effect of short- and long-term administration of lithium on the release of endogenous 5-HT in the hippocampus of the rat in vivo and in vitro.

The present study determined the effect of short- (3 days) and long- (21 days) term treatment with lithium on the release of 5-hydroxytryptamine (5-HT) form the hippocampus of the rat, measured both in vivo using microdialysis and in vitro using incubated slices. In the in vivo experiments (on the chloral hydrate-anaesthetized rat) electrical stimulation of the dorsal raphe nucleus for 20 min evoked an increase of 5-HT in dialysates of hippocampus, which both lasted for the duration of the stimulus and was frequency-dependent (2-10 Hz). Electrical stimulation of the dorsal raphe nucleus, at low stimulation pulse frequencies (2 and 3 Hz), released 3-4 fold more 5-HT in rats treated for 3 days with lithium chloride (3 mmol/kg s.c. twice daily), compared to controls. However, the effect of stimulation of the dorsal raphe nucleus was not altered in rats receiving lithium in the diet for 21 days. Basal levels of 5-HT in hippocampal dialysates for rats receiving long- but not short-term treatment with lithium, were significantly lower than controls. In agreement with the in vivo experiments, the in vitro experiments showed that depolarization (high potassium)-evoked release of endogenous 5-HT from slices of hippocampus of rats treated with short- but not long-term administration of lithium was enhanced compared to controls. These experiments provide direct biochemical evidence that short-term treatment with lithium increases depolarization-evoked release of endogenous 5-HT in the hippocampus, an effect which may be related to the rapid antidepressant actions of the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Nutrient balance in humans: effects of diet composition.

The purpose of this study was to examine the effect of alterations in diet composition on energy expenditure and nutrient balance in humans. Eight adults (three men, five women) ate a high-carbohydrate (60% of calories from carbohydrate) and a high-fat (60% of calories from fat) diet for 7 d each according to a randomized, crossover design. Six subjects were studied for an additional week on a mixed diet (45% of calories from fat). For each subject, total caloric intake was identical on all diets and was intended to provide the subject's maintenance energy requirements. All subjects spent days 3 and 7 of each week in a whole-room indirect calorimeter. Diet composition did not affect total daily energy expenditure but did affect daily nutrient oxidation by rapidly shifting substrate oxidation to more closely reflect the composition of the diet. These results show that diet composition can affect substrate oxidation without producing measurable effects on total energy expenditure.

Adult↗
PubMed1990

Further investigation of the in vivo pharmacological properties of the putative 5-HT1A antagonist, BMY 7378.

The present study examined the actions of the putative 5-HT1A antagonist BMY 7378 on central pre- and postsynaptic 5-HT1A function in the rat in vivo. Unlike the direct acting 5-HT1A agonist 8-hydroxy-2-(di-n-pro-pylamino)tetralin (8-OH-DPAT), BMY 7378 (0.25-5 mg/kg s.c.) did not induce the full postsynaptically mediated 5-HT behavioural syndrome (forepaw treading, head weaving, flat body posture hindlimb abduction). Indeed, the maximal 5-HT behavioural syndrome scores of BMY 7378 were about 10% of those for 8-OH-DPAT. Following pretreatment, however, BMY 7378 dose dependently (0.25-5 mg/kg s.c.) reduced to undetectable levels forepaw treading and head weaving induced by 8-OH-DPAT (0.75 mg/kg s.c.). BMY 7378 also inhibited stereotypy and locomotor activity induced by 0.5 mg/kg apomorphine although this effect was only statistically significant at the highest dose tested (5 mg/kg). In contrast to its apparent 5-HT1A antagonist properties in the behavioural experiments, BMY 7378 caused a marked and dose-dependent (0.01-1.0 mg/kg s.c.) decrease of 5-HT release in ventral hippocampus of the anaesthetized rat as detected by brain microdialysis. This effect of BMY 7378 had a similar onset and duration of action but with slightly reduced efficacy compared to that previously described for 8-OH-DPAT. As with 8-OH-DPAT, the inhibitory effect of BMY 7378 on 5-HT release was attenuated by pretreatment with the 5-HT1 receptor/beta-adrenoceptor antagonist pindolol (8 mg/kg s.c.) but not its counterpart propranolol (20 mg/kg s.c.). Pretreatment with a combination of the beta 1- and beta 2-adrenoceptor antagonists metoprolol (4 mg/kg s.c.) and ICI 118 551 (4 mg/kg s.c.), respectively, did not alter the 5-HT response to BMY 7378. From these data we conclude that BMY 7378 is a mixed agonist/antagonist at central 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

cis-(+)-8-OH-1-CH3-DPAT, (+)ALK-3, a novel stereoselective pharmacological probe for characterizing 5-HT release-controlling 5-HT1A autoreceptors. An in vivo brain microdialysis study.

The somatodendritic 5-HT1A autoreceptor regulating 5-HT neuronal activity is currently poorly defined pharmacologically because there are no specific antagonists, but also because potent and stereoselective agonists are scarce. Moreover, there have been few, if any, attempts to specifically investigate structure-activity relationships for agonists acting at this site. Employing brain microdialysis techniques, we have examined the effects of the enantiomers of cis-8-hydroxy-1-methyl-2-(di-n-propylamino)tetralin (ALK-3; 0.01-0.3 mg/kg s.c.), its trans-1-methyl analogue (ALK-4; 0.3 mg/kg s.c.) and the pure enantiomers of the parent compound--8-OH-DPAT (0.3 mg/kg s.c.)--in an attempt to address stereochemical agonist structure-activity requirements of 5-HT release-controlling 5-HT1A autoreceptors in brain. The cis-1-methylated 8-OH-DPAT analogue (+)ALK-3 was comparable to the parent compound in reducing the 5-HT output from rat ventral hippocampus. In comparison, both (-)ALK-3 and the racemic trans-diastereomer to ALK-3, ALK-4, were inactive, while the two stereoisomers of 8-OH-DPAT strongly reduced 5-HT release. Pretreatment with (-)pindolol (8 mg/kg s.c.), which has high affinity for 5-HT1A radioligand binding sites, blocked the reduction of hippocampal 5-HT release induced by a submaximally effective dose of (+)ALK-3. The direct intrahippocampal administration of (+)ALK-3 (10 microM) via the perfusion medium did not affect 5-HT output. In summary, the data indicate that (+)ALK-3, like 8-OH-DPAT, is a very potent 5-HT receptor agonist which inhibits terminal 5-HT release in rat hippocampus, probably via activation of somatodendritic 5-HT1A autoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗