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T F Lee

Publications and source records attributed to T F Lee.

At least 55 records · Page 3Linked to original sources
PubMed1984

Calmodulin-induced feeding in the satiated cat: evidence for involvement of calcium and norepinephrine in the brain.

The central effect of the Ca++ binding protein, calmodulin (CaM) on spontaneous feeding as well as on core temperature was examined in the satiated cat in which chronically indwelling cannulae were permanently implanted for intracerebroventricular (ICV) infusion. When CaM was injected ICV in doses of 2.5-10.0 micrograms, the intake of food was significantly enhanced in the satiated cat without any notable change in the animal's core temperature. Ca++ ions infused similarly in a solution of 6.25-25.0 mM also augmented the spontaneous ingestion of food, which was accompanied by a concentration-related decline in core temperature. When infused separately, neither CaM in a low dose (1.25 micrograms) nor Ca++ ions (3.0 mM) given ICV altered the intake of food of the satiated cat. However, the simultaneous infusion of CaM and Ca in these concentrations enhanced significantly the amount of food consumed by as much as 60 g. When the same concentration of Ca++ ions was infused ICV simultaneously with 5.0 micrograms troponin C, a Ca++ binding protein of an identical molecular weight, the intake of food was unaltered. Further, the spontaneous feeding induced by CaM could be attenuated either by the central chelation of Ca++ ions by 1.0-1.5 mM EGTA or by 30 micrograms calcineurin, a specific CaM inhibitor, when either was given ICV. Pre-treatment of the cat with ICV phentolamine (50 micrograms) also reduced the CaM-induced feeding response significantly, whereas the similar pre-treatment with ICV propranolol (50 micrograms) or naloxone (100 micrograms) failed to affect CaM-induced feeding behavior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Calmodulin-induced feeding in the cat: attenuation by calcium chelator EGTA.

Cannulas for intracerebroventricular injection of calmodulin (CaM), Ca2+, and other substances were implanted stereotaxically in the cat. Postoperatively, measures of food intake were taken on each day during a 1.0-h interval until feeding had stabilized. Then the Ca2+-binding protein, CaM, was infused intracerebroventricularly into the fasted cat 15 min before the 1.0-h feeding session. CaM (0.15-0.60 nM) significantly enhanced the animal's normal feeding response, which was accompanied by a slight decline in body temperature. Infusion of 6.25-50.0 mM excess Ca2+ reduced body temperature in a concentration-dependent manner with food intake augmented by 6.25-25.0 mM Ca2+. Chelation of Ca2+ in the brain with 0.5-2.5 mM ethyleneglycol-bis(beta-aminoethyl ether)-N,N'-tetra-acetic acid (EGTA) similarly infused intracerebroventricularly into the cat simultaneously suppressed feeding and elevated core temperature. Threshold doses of EGTA selectively attenuated CaM-induced eating but not feeding elicited by the catecholamine neurotransmitter, norepinephrine. Overall these results suggest that CaM, by complexing with cellular Ca2+, could serve as an intermediary factor in governing steady-state activity of neurons in the brain. In turn, this essential cation may mediate specific regulatory processes within the diencephalon that underlie the postulated "setpoint" mechanism for the control of feeding.

Animals↗
PubMed1983

Calmodulin infused intracerebroventricularly enhances food intake in the cat.

In the fasted cat, calmodulin (CaM) infused into the cerebral ventricle produces an increase in the normal intake of food in a dose-dependent manner. The enhancement of feeding by CaM seems to be functionally specific since the response was: (1) abolished by the simultaneous intraventricular infusion of calcineurin, a specific CaM antagonist; (2) not mimicked by another calcium binding protein, troponin C; and (3) independent of the CaM's lack of effect on body temperature and water intake. This finding opens up the dual possibility that this Ca2+ binding protein may affect receptors other than intracellularly and that CaM is involved in specific functions controlled by the brain.

Animals↗
PubMed1983

Evaluation of neurotensin's thermolytic action by ICV infusion with receptor antagonists and a Ca++ chelator.

To investigate the mechanisms responsible for the thermolytic action of neurotensin (NT), cannulae for intracerebroventricular (ICV) injection were implanted stereotaxically in Sprague-Dawley rats. Postoperatively, body temperature in the unrestrained rat was monitored continuously by a colonic thermistor probe. NT in a dose of 1.5-4.5 micrograms or CSF carrier vehicle was infused bilaterally in the cerebral ventricle (ICV) in a volume of 7.5 microliters. With the rats kept at an ambient temperature of 22 degrees C, NT given ICV produced a dose-dependent fall in core temperature of greater than 0.8 degree C. Pre-treatment of the animal's cerebral ventricle with amine receptor antagonists, phentolamine (20.0 micrograms), butaclamol (10.0 micrograms), methysergide (20.0 micrograms) or atropine (25.0 micrograms), all similarly infused ICV, failed to alter the hypothermia induced by NT. However, the calcium chelating agent, EGTA, given ICV in a dose of 4.0-8.0 micrograms blocked the thermolytic effect of NT on body temperature in a concentration-dependent manner. These results suggest that the central thermolytic action of NT is not mediated by catecholamine or other aminergic pathways which are implicated in the central mechanisms of thermoregulation. Rather, the peptide may act on a cellular process involving calcium activity in the hypothalamus, presumably to impair the maintenance of the animal's "set-point" for body temperature.

Animals↗
PubMed1983

Analysis of the thermolytic action of ICV neurotensin in the rat at different ambient temperatures.

Intracerebroventricular (ICV) cannulae were implanted chronically in adult female Sprague Dawley rats for central injection of neurotensin (NT) or artificial CSF vehicle. During experiments carried out at 48 hr intervals, the body temperature of each rat was monitored continuously by a thermistor probe inserted in the colon. At an ambient temperature of 22 degrees C, NT infused ICV in a threshold dose of 1.5 micrograms caused a mean maximum fall of 0.9 degrees C in the rats' body temperature. This decline in core temperature was enhanced further to 1.4 degrees C when the rats were exposed to an ambient temperature of 4 degrees C for 1.0 hr immediately after the NT infusion. Similarly, when the rats were exposed to 34 degrees , 36 degrees or 40 degrees C, again for 1.0 hr directly after NT administration, core temperature increased to a maximum of 0.3 degrees to 0.6 degrees during this interval. The maximum hyperthermic response following the control ICV infusion of CSF in rats exposed to the same elevated ambient temperatures was slightly greater (0.2-0.3 degrees C) than that after infusion of NT, because of the initial thermolytic effect produced by the peptide. However, the respective slope of each rise in body temperature in both NT and CSF groups during exposure to all three warm temperatures was nevertheless identical. Overall, the results show that in the animal given NT centrally the core temperature tends to follow the ambient temperature, either cold or warm. Thus, it is concluded that NT possesses a clear-cut poikilothermic action on the central neutral systems underlying the control of body temperature. Therefore, it remains uncertain whether NT in fact could play any role in the mechanism within the diencephalon which mediates normal thermoregulatory function.

Animals↗
PubMed1983

Involvement of alpha- and beta-adrenoreceptors in the central action of norepinephrine on temperature, metabolism, heart and respiratory rates of the conscious primate.

The effect of the central blockade of alpha- and beta-adrenoreceptors on the action of norepinephrine (NE) infused by the intracerebroventricular (ICV) route was examined in the unanesthetized primate. After cannulae for ICV infusion were implanted sterotaxically, each monkey (Macaca fasicularis) was placed in a restraint chair fitted with a transparent dome for measurement of O2 uptake. During an experiment, the following responses were monitored simultaneously on a polygraph: skin and colonic temperatures, heart and respiratory rates, and metabolic rates as reflected by O2 uptake. Following an ICV infusion of 150 micrograms NE, colonic temperature, heart and metabolic rates declined while skin temperature increased and respiratory rate remained unchanged. Pretreatment with ICV phentolamine (100 micrograms), an alpha-adrenoreceptor antagonist, attenuated the changes in temperature, heart and metabolic rates and reduced respiratory rate. Similar ICV infusion of 100 micrograms propranolol, a beta-adrenoreceptor antagonist, tended also to attenuate the responses induced by NE, but overall was much less efficacious than phentolamine. Our results indicate that although catecholaminergic neurons mediate these vital physiological processes principally by central alpha-adrenoreceptors, a substantial beta-adrenoreceptor component also participates in the mechanism responsible for specific functional changes.

Animals↗
PubMed1983

A role for an indoleamine other than 5-hydroxytryptamine in the hypothalamic thermoregulatory pathways of the rat.

1. Intrahypothalamic injection of either 5-hydroxytryptamine (5-HT) (20 mug) or tryptamine (1 mug) caused hypothermia and hyperthermia respectively in lightly restrained rats maintained at an ambient temperature of 20 +/- 1 degrees C.2. Both the 5-HT- and the tryptamine-sensitive sites were located within the same region of the preoptic area.3. When rats were tested at different ambient temperatures (4, 20 and 29 degrees C), intrahypothalamic injection of 5-HT caused a marked fall in core temperature (-1.3 degrees C) in rats maintained at 4 degrees C, but smaller responses were obtained at 20 and 29 degrees C (-0.9 and -0.5 degrees C respectively). Tryptamine caused a significant hyperthermia in rats kept at 20 degrees C, but had no significant effect in rats maintained at either 4 or 29 degrees C.4. The hypothermic effect of 5-HT was selectively antagonized by systemic pre-treatment with cyproheptadine (2.5 mg/kg), but not by methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg). In contrast, the hyperthermic effect of tryptamine was blocked by methergoline and methysergide, but not by cyproheptadine.5. Cyproheptadine (2.5 mg/kg) reduced the ability of rats to cope with a heat load but had no effect on the response to cold. In contrast, methergoline (0.625 mg/kg) and methysergide (0.2 mg/kg) reduced the ability to cope with cold but the rats' ability to cope with a heat load remained intact.6. These results suggest the existence of two indoleamine pathways within the preoptic anterior hypothalamus involved in the control of body temperature: a serotonergic pathway mediating heat loss and a non-serotonergic pathway mediating heat gain. The non-serotonergic system may exert its effects by modulating the activity of a central serotonergic system.

Animals↗
PubMed1982

Involvement of a central dopaminergic system in 5-methoxy-N,N-dimethyltryptamine-induced turning behaviour in rats with lesions of the dorsal raphé nuclei.

The turning behaviour induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) has been investigated in rats with lesions of the dorsal raphé nucleus (DRN). 5-MeODMT caused a dose-related contralateral turning in rats with 5,7-dihydroxytryptamine (5,7-DHT) lesions of the substantia nigra and a similar effect was observed in DRN-lesioned rats. In contrast, a dose-related ipsilateral turning was observed when 5-MeODMT was injected into rats with 5,7-DHT lesions of the striatum. These results suggest that the effects of 5-MeODMT in DRN-Lesioned rats are mediated via the substantia nigra. The contralateral turning induced by 5-MeODMT in rats with a 5,7-DHT lesion of the DRN was significantly reduced when a second 5-hydroxydopamine lesion was placed in the striatum, but not when it was placed in the nucleus accumbens. Thus the nigrostriatal dopaminergic system seems to be involved in 5-MeODMT-induced turning. The release of tritium from slices of substantia nigra previously labelled with [3H]-dopamine was inhibited by 5-MeODMT (10(-7) to 10(-5) M) and this effect was blocked by methysergide in a concentration-related manner. Tetrodotoxin (10(-7) M) failed to antagonise 5-MeODMT. These results suggest that 5-MeODMT can inhibit dopamine release from nigral dendrites, which could in turn enhance nigrostriatal activity by reducing the auto-inhibitory actions of dopamine, thereby causing contralateral turning in DRN-lesioned rats.

5,7-Dihydroxytryptamine↗
PubMed1982

Unique contribution of catecholamine receptors in the brain of the cat underlying feeding.

After a Collison cannula was implanted bilaterally in the cat for intracerebroventricular (ICV) injection, individual patterns of food intake were determined. A mixture of dry and canned cat food was provided to the animal every morning at the same time for 1.0 hr. Once intakes had stabilized, either norepinephrine (NE) or an adrenoreceptor blocking agent was infused in one lateral ventricle by gravity flow over an interval of 30-60 sec. NE given ICV in a dose of 25-75 micrograms 15 min before the period of feeding enhanced both the amount of food consumed by the cat and the duration of its feeding for up to 1.0 hr. When phentolamine in a dose of 25-100 micrograms was infused 15 min prior to the feeding interval, the cat's intake of food was attenuated in a dose-dependent manner, again in terms of both the quantity consumed and the interval of eating. Propranolol was essentially without effect on food intake. In the fully satiated cat, NE infused ICV 15-45 min following the termination of its morning feeding episode tended to augment food intake at the highest 100 micrograms dose, but the effect was not significant. The dose-dependent hypothermia typically observed after NE is given ICV to the cat was found to be entirely independent of the feeding response. Overall, these findings show that noradrenergic pathways in the cat's feeding system apparently bias or otherwise modulate the amount of food consumed. As in other species, the feeding mechanism appears to be mediated through alpha-adrenergic receptors presumed to be in the diencephalon of the cat.

Animals↗
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↗
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

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

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↗
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↗