Biomedical subjects

D V Coscina

Publications and source records attributed to D V Coscina.

At least 37 records · Page 2Linked to original sources

PubMed1995

Ineffectiveness of hypothalamic serotonin to block neuropeptide Y-induced feeding.

A variety of recent research has suggested that the feeding associated with enhanced neuropeptide Y (NPY) activity within the hypothalamus may operate in part by interacting antagonistically with other neural processes responsive to serotonin (5-hydroxytryptamine or 5-HT). To test this possibility further, experiments were performed to determine if the magnitude of feeding produced by injecting NPY into the paraventricular nucleus (PVN) or the perifornical hypothalamus (PFH) was diminished by coinjections of 5-HT into these two sites or peripheral injections of the 5-HT agonist, d-fenfluramine. Adult male Sprague-Dawley rats were implanted unilaterally with stainless steel cannulae aimed to terminate either in the PVN or the PFH. In both studies, NPY (235 pmol) produced significant feeding in both sites either 1 or 2 h after injection when compared to saline. This enhanced feeding response was significantly greater in the PFH 2 h after injection (40% in the central study; 70% in the peripheral study). Coinjection of 5-HT (6.3, 12.5, or 25.0 nmol) into either site had no effect on the induction of this NPY-induced feeding response. However, peripherally injected d-fenfluramine (0.32, 0.63, or 1.25 mg/kg) produced strong dose-dependent attenuation both 1- and 2-h food intake elicited by 235 pmol NPY in either site, with the PFH being proportionately more sensitive to this effect. Viewed together, these results suggest that the feeding-suppressant effects of systemic fenfluramine on hypothalamic NPY-induced feeding may operate largely via peripheral mechanisms and/or central ones that have little to do with its 5-HT agonistic effects within the PVN or PFH.

Animals↗

PubMed1995

Dissociated feeding and hypothermic effects of neuropeptide Y in the paraventricular and perifornical hypothalamus.

The present study investigated the effects of neuropeptide Y (NPY) on food intake and body temperature (Tbo) in free-feeding unrestrained rats following injection into the medial hypothalamic paraventricular nucleus (PVN) or the lateral perifornical hypothalamus (PFH). NPY (78-235 pmol) or saline was infused unilaterally into the PVN or PFH in a volume of 0.4 microliter and simultaneous measures of food intake and Tbo were taken every 30 min for 3 h. Results indicated that NPY evoked changes in eating behavior and Tbo that were dependent upon the site of hypothalamic injection. Although PVN and PFH administration of NPY both increased food intake dose dependently within 30 min of treatment, PFH NPY-injected rats (n = 9) showed a stronger behavioral response compared to rats (n = 9) receiving NPY injections into the PVN. In PVN-treated rats, however, the increased eating was associated with a significant decline in Tbo evident within the first 30-min test interval. A mean maximal decline of 0.92 +/- 0.26 degree C occurred within 90 min of PVN treatment of the highest dose, which produced a reduction in Tbo that was maintained for 2.5 h. In contrast, NPY infusion into the PFH failed to reliably alter Tbo at any of the doses tested. These findings are consistent with evidence that NPY in the PVN and PFH may have distinct functions and suggest that although PFH NPY acts to stimulate a robust and relatively specific ingestive response, PVN NPY may participate in the complex integrative mechanisms responsible for the simultaneous regulation of feeding, thermoregulatory, and metabolic processes.

Animals↗

PubMed1994

Brain and behavioral effects of dietary n-3 deficiency in mice: a three generational study.

Feeding mice a diet deficient in n-3 fatty acids for three generations resulted in a 53% decrease in docosahexaenoic acid (DHA, 22:6n-3) in the brain. Maternal pup retrieval and social learning of a food preference are both tasks based on olfactory function. All dams made contact more readily with pups of their own dietary group, and animals of both dietary groups demonstrated the ability to learn a food preference through exposure to a conspecific that had previously eaten the food. Both groups showed similar ability to learn the location of the hidden platform in the Morris water maze, while the n-3 deficient animals were marginally faster in locating the platform on the cued trial. They were also more active when tested in the open field. While they did not differ in their duration of immobility in a forced swimming test, the deficient animals did have longer paw-lick latencies on a hot plate. Thus, in this study a significant reduction in brain n-3 fatty acid composition, while associated with some indications of change in emotional reactivity, did not impair olfactory function or learning of either a latent or spatial nature.

Animals↗

PubMed1994

Intraventricular but not intraparaventricular nucleus metergoline elicits feeding in satiated rats.

Previous research has shown that systemic injections of the nonselective serotonin (5-HT) antagonist metergoline (MET) can stimulate feeding in both rats and humans. Five experiments were conducted to determine if this drug would elicit feeding in otherwise satiated rats after direct injections into the brain. In experiment 1, intraventricular infusions of 100 nmol MET produced reliable enhancements of feeding for 1 h compared with control infusions of a 5% tartaric acid (vehicle) solution. In experiment 2, a dose-response study of 0, 50, 100, and 150 nmol MET intraventricularly revealed that both 100 and 150 nmol doses reliably enhanced 1-h feeding, whereas 50 nmol did not. In experiment 3, tests of 90-min locomotor activity and water intake in the absence of food revealed that 100 nmol MET intraventricularly did not modify either behavior compared with vehicle infusions, suggesting a degree of feeding specificity to this effect. In an attempt to determine the site of intraventricular MET effects on feeding, experiment 4 tested 1-h feeding responses after 0, 5, 10, 20, 40, or 60 nmol MET were infused unilaterally into the paraventricular nucleus (PVN) of the hypothalamus. No reliable feeding was induced at any of these drug doses, although injections of 30 nmol norepinephrine (NE) were effective in doubling food intake. Experiment 5 further showed that bilateral infusions of 50 nmol MET in each PVN (total dose, 100 nmol) were ineffective in altering 1-h feeding. This contrasted markedly to the high potency of 15 nmol NE per site (total dose, 30 nmol), which elicited fivefold greater feeding than control infusions.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Administration of 8-OH-DPAT into the midbrain raphe nuclei: effects on medial hypothalamic NE-induced feeding.

The 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) has been shown to elicit dose-dependent feeding in satiated rats when injected into the midbrain raphe nuclei. Because the feeding-stimulatory effects of this compound are associated with reduced 5-HT release in forebrain, and because recent evidence suggests that medial hypothalamic norepinephrine (NE) and 5-HT may function antagonistically in the control of feeding, the present study sought to determine whether 8-OH-DPAT would enhance feeding induced by infusing NE into the medial hypothalamus. All experiments were conducted using ad libitum-fed adult male rats with two indwelling cannulas, one aimed at the paraventricular nucleus (PVN), the other at either the dorsal or median raphe. In the first series of experiments rats received a fixed dose of 8-OH-DPAT (0.8 nmol) microinjected into the dorsal or median raphe, as well as NE (0, 10, 20 nmol) administered into the PVN. In the second series, rats received varying doses of raphe 8-OH-DPAT (0, 0.4, 0.8 nmol) coinjected with a single dose of PVN NE (20 nmol). Results indicated that 8-OH-DPAT and NE both elicited reliable increases in 1-h food intake, although their effects did not interact. In the final series, rats were injected with subthreshold doses of both compounds. While combined injections of 8-OH-DPAT and NE modestly increased feeding compared with saline control, this increase was not significantly greater than intake found after injection of 8-OH-DPAT or NE alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1994

Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats.

Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

Adrenalectomy↗

PubMed1993

Radiofrequency lesions of the PVN fail to modify the effects of serotonergic drugs on food intake.

Past research has suggested that the paraventricular nucleus (PVN) of the hypothalamus is an important brain site mediating changes in feeding induced by drugs that modify 5-hydroxytryptamine (5-HT; serotonin) neurotransmission. To test this possibility, several experiments examined the impact of lesions of the PVN on both decreases and increases in feeding following treatment with 5-HT-acting drugs. Rats with free access to standard lab chow were given access also to a wet mash diet for 1 h each day. When intakes of this diet had stabilised, rats were divided into two groups: one group received bilateral radiofrequency lesions of the PVN, the other served as a sham-operated control group. The PVN-lesioned group consumed more lab chow and gained significantly more weight over a 10-week period than the control group. Clonidine stimulated feeding in the sham-operated group, but did not do so in the lesioned group. These findings confirmed that the PVN lesions disrupted the control of food intake, as well as body weight regulation. The indirect 5-HT agonists D-fenfluramine (0.63, 1.25 and 2.5 mg/kg) and fluoxetine (2.5, 5 and 10 mg/kg), and the 5-HT1 agonist 1-(m-trifluoromethylphenyl)piperazine (TFMPP, 0.63, 1.25 and 2.5 mg/kg) dose dependently reduced the intake of the wet mash diet in sham-operated animals. This action was not modified by the PVN lesions. The highest doses of D-fenfluramine and fluoxetine also suppressed intake of chow over the 23-h period subsequent to the wet mash presentations, but the magnitude of this effect was similar in sham-operated and PVN-lesioned animals.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1993

Paraventricular nucleus injections of idazoxan block feeding induced by paraventricular nucleus norepinephrine but not intra-raphe 8-hydroxy-2-(di-n-propylamino)tetralin.

Previous work has shown that injection of the 5-hydroxytryptamine (5-HT)1A agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) into the midbrain raphe nuclei activates somatodendritic 5-HT autoreceptors leading to decreased 5-HT synthesis and release in terminal forebrain regions and an increase in feeding behaviour. Since 5-HT is believed to function antagonistically with norepinephrine (NE) in the hypothalamic paraventricular nucleus (PVN) to control feeding, it has been proposed that 8-OH-DPAT elicits food intake by removing the inhibitory influence of 5-HT over PVN alpha 2-adrenergic feeding mechanisms. This hypothesis was tested by examining the ability of PVN injection of the alpha 2-adrenoceptor antagonist idazoxan (IDAZ) to attenuate the feeding stimulant action induced by raphe injection of 8-OH-DPAT. In the first series of experiments the dose-response effects of dorsal and median raphe injection of 8-OH-DPAT in addition to PVN NE on feeding were examined. Injection of NE (5-40 nmol) and 8-OH-DPAT (0.4-1.6 nmol) both elicited reliable dose-dependent increases in 1 h food intake compared to saline control. Similar doses of 8-OH-DPAT injected into the PVN failed to alter baseline feeding. A second series of experiments examined the effects of IDAZ on 8-OH-DPAT and NE-stimulated food intake in rats implanted with dorsal or median raphe cannulae as well as cannulae aimed at the PVN.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1993

Lack of synergistic feeding enhancement by systemic clonidine and 8-OH-DPAT.

To expand on recent suggestions that brain alpha 2-adrenergic and serotonergic systems may interact in their controls over feeding, three experiments were conducted to determine if combining clonidine and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) injections subcutaneously might produce exponential feeding enhancements greater than responses elicited by either agent alone. Ad lib fed adult male rats were tested in 2 x 2 drug designs in all studies. In Experiment 1, 30 micrograms/kg clonidine reliably enhanced feeding over a 6-hr test period. However, 250 micrograms/kg 8-OH-DPAT showed no signs of enhancing this response, but instead seemed to impede it as determined by analyses of cumulative intake curves. In Experiment 2, either 10 micrograms/kg clonidine or 250 micrograms/kg 8-OH-DPAT reliably enhanced 6-h interval intakes, but their combination again failed to synergize other than to interact with time in suppressing intake. To determine if feeding synergy might occur if subthreshold doses of each agent were combined, Experiment 3 tested 1 microgram/kg clonidine and 15 micrograms/kg 8-OH-DPAT in 4-h feeding tests. Neither agent alone elicited reliable feeding as planned, but their combination also failed to stimulate feeding. These findings, combined with other recent work, do not support the possibility that previously demonstrated interactions between brain alpha 2-adrenergic and serotonergic systems extend to circumstances wherein enhancements of the former combined with suppressions of the latter might underly robust overeating responses.

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

PubMed1993

Injecting 5-HT into the PVN does not prevent feeding induced by injecting 8-OH-DPAT into the raphe.

The selective 5-hydroxytryptamine1A (5-HT1A) agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) activates raphe somatodendritic autoreceptors, leading to an inhibition of 5-HT neuronal activity and reduced synthesis and release of 5-HT in forebrain terminal areas. One behavioural consequence of this is increased feeding in satiated rats. Because injections of 5-HT agonists into the medial hypothalamus suppress feeding, it has been proposed that 8-OH-DPAT-induced feeding may involve a reduction of 5-HT release within this area. This hypothesis was tested by examining the ability of 5-HT injected into the medial hypothalamus to reverse the feeding-stimulant action of 8-OH-DPAT following injection into the dorsal raphe or median raphe. Two groups of rats, maintained with free access to food at all times, were used. Each was prepared with two cannulae, one aimed at the paraventricular nucleus (PVN) of the medial hypothalamus and the other at either the dorsal raphe nucleus or median raphe nucleus. Food intake over the next hour was increased following dorsal raphe or median raphe injections of 8-OH-DPAT (1 and 0.5 microgram, respectively). These effects were not blocked by injections of 7.5 or 15 micrograms 5-HT into the PVN. However, 15 micrograms 5-HT did attenuate the feeding-stimulant action of 10 micrograms norepinephrine injected into the PVN. These results do not support the hypothesis that a reduction in 5-HT release within the medial hypothalamus is responsible for the feeding-stimulant action of 8-OH-DPAT.

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

PubMed1993

Research on "feeding behavior": quantitative information vs. qualitative perceptions about where it is published.

To gain some understanding of where research on "feeding behavior" is published, a Medline search was conducted for the years 1980-1990 inclusive using the above key phrase to capture published articles coded in this way. Furthermore, an eight-item questionnaire was mailed to all 451 persons listed in the 1990 membership directory of the Society for the Study of Ingestive Behavior (SSIB) soliciting views on the top five journals publishing the greatest number, as well as the most "prestigious," articles in this field, along with demographic information about the respondents. After deleting journals that published agriculturally based research relating to insects or parasites, the Medline search generated 1,813 articles in the top 25 journals, the top 5 of which were Physiology and Behavior (462 articles), Pharmacology, Biochemistry and Behavior (211 articles), Brain Research (118 articles), American Journal of Physiology (106 articles) and Brain Research Bulletin (87 articles). This fact accorded well with weighted scores generated from perceptions of SSIB respondents (24.4% return rate), whose top 25 rankings correlated highly (r14 = +0.829, p < .001) with the Medline data. Although the top 5 number 1 choices of "prestige" journals by SSIB members did not match up well with the Medline list, weighted "prestige" scores correlated reasonably well with the Medline data (r15 = +0.766, p < .001), but a bit less so with SSIB perceptions of where greatest numbers of articles appeared (r12 = +0.588, p < .05). Discussion is presented about the validity of these data, their implications, and their potential utility in helping researchers decide where to publish work in this field.

Animals↗

PubMed1993

Diurnal variations in the feeding response to 8-OH-DPAT injected into the dorsal or median raphe.

To determine the impact on food intake of the 5-HT1A agonist, 8-OH-DPAT, administered at various times throughout the nocturnal cycle, rats were implanted with cannulae in either the dorsal or median raphe nuclei and injected with saline or 8-OH-DPAT (0.4, 0.8 or 1.6 nmol) immediately following dark onset, or during the mid or late dark periods. 8-OH-DPAT potentiated feeding when administered in the mid or late dark phase, whereas treatment during the early dark actually suppressed food intake. These findings indicate that the feeding responses to dorsal and median raphe 8-OH-DPAT vary greatly depending on the time of administration in the diurnal cycle and are consistent with recent reports of a biphasic action of this compound on ingestive behaviour.

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

PubMed1992

Effects of intracisternal vs. intrahypothalamic 5,7-DHT on feeding elicited by hypothalamic infusion of NE.

A variety of evidence has led to suggestions that brain serotonin (5-HT) and norepinephrine (NE) interact within the medial hypothalamus to control food intake. To test the possibility that chronic decrements in 5-HT might enhance NE-induced feeding, adult male rats were prepared with permanently indwelling cannulae aimed at the paraventricular nucleus (PVN), then received either intracisternal (IC) or PVN injections of the 5-HT neurotoxin, 5,7-dihydroxytryptamine (5,7-DHT) vs. its vehicle, 1% ascorbic acid. Over a 4-week period, IC-5,7-DHT rats showed no signs of enhanced daily feeding or drinking. However, in 40-min intake tests, feeding but not drinking was enhanced by injecting 20 nmol NE into the PVN commencing 2 weeks after neurotoxin treatment. Terminal monoamine assays confirmed that IC-5,7-DHT produced large (80-90%) depletions of brain regional 5-HT. A functional index of 5-HT terminal damage was also implied by the impaired short-term feeding responses IC-5,7-DHT rats showed to the systemic administration of the 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) when tested between 3 and 4 weeks after IC treatment. Over a comparable 4-week period, PVN-5,7-DHT rats also showed no tendencies to overeat or overdrink on a daily basis. However, in contrast to IC-5,7-DHT rats, they also showed no differences in their feeding or drinking responses to NE injections into the PVN. This was so despite reliable depletions of 5-HT in the hypothalamus (-28%) and hippocampus (-71%). These results support earlier work showing that neither widespread nor localized hypothalamic damage to brain 5-HT neurons produce chronic overeating. However, the data suggest that phasic enhancements of PVN NE activity may trigger enhanced feeding when there is widespread damage to brain 5-HT neurons, although the PVN does not appear to be the brain site mediating this effect.

5,7-Dihydroxytryptamine↗

PubMed1992

A comparison of the effects of the 5-HT1 agonists TFMPP and RU 24969 on feeding following peripheral or medial hypothalamic injection.

Experiments were conducted to compare the food intake suppressant effects of the 5-hydroxytryptamine (5-HT)1 agonists 1-3-trifluoromethylphenylpiperazine hydrochloride (TFMPP) and 5-methoxy-3-(1,2,3,6-tetrahydropyridinyl)1H indole (RU 24969) following either peripheral or medial hypothalamic injections. The effects of these manipulations were examined in 3 different paradigms involving the stimulation of feeding by: (1) infusion of 25 nmol noradrenaline (NA) into the medial hypothalamus, (2) adaptation to a 20 h food deprivation schedule, and (3) the presentation of a palatable wet mash diet for 1 h each day to ad libitum-fed rats. In all 3 paradigms TFMPP and RU 24969 (0.31-5 mg/kg, i.p.) induced dose-dependent reductions of food intake. Both drugs were somewhat less potent at inhibiting feeding that resulted from food deprivation. In contrast to these results medial hypothalamic infusion of TFMPP or RU 24969 (12.5-50 nmol) failed to affect food intake in any of the 3 tests. This occurred in spite of the fact that both 5-HT (12.5-50 nmol) and fluoxetine (12.5-50 nmol) mildly attenuated the feeding that resulted from NA infusion into the same site. The results provide clear evidence that the food intake suppressant effects of peripherally injected TFMPP and RU 24969 are not mediated in the medial hypothalamus. They also suggest that even though manipulations of serotonergic function within the medial hypothalamus can alter food intake, this probably does not involve selective activation of 5-HT1C and/or 5-HT1B receptors.

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

PubMed1992

Effects of increasing brain GABA on the meal patterns of genetically obese vs. lean Zucker rats.

To explore recent suggestions that genetically obese Zucker rats show less anorexia when brain gamma-aminobutyric acid (GABA) is elevated, obese vs. lean littermates received 100, 50 and 0 micrograms of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), intra-cisternally in a longitudinal design where their feeding patterns were monitored 24 h daily. Obese rats were refractory to EOS-induced anorexia as evidenced by less suppression of daily food intake and fewer alterations to both meal size and meal frequency, particularly in the night. This effect was not due to an inability of EOS to increase brain GABA since equivalent, specific dose-dependent increments were seen in the brains of separate obese vs. lean rats after analysis of endogenous GABA and seven other amino acids. An unexpected finding was elevated levels of brain taurine for obese rats regardless of EOS dosage, implying a hitherto unknown neurochemical trait whose potential significance is unclear. The primary data obtained provide further support for recent hypotheses that obese Zucker rats possess altered brain GABAergic mechanisms that may serve as one contributor to their over-eating.

Animals↗

PubMed1991

Influence of taste and food texture on the feeding responses induced by 8-OH-DPAT and gepirone.

Previously it has been shown that 5-hydroxy-tryptamine (5-HT)1A agonists such as 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) and gepirone increase food intake in free-feeding rats. These experiments were conducted to examine the possible influence of taste and textural factors on the feeding responses induced by these two drugs. Separate groups of non-water-deprived rats were given access to one of a variety of different solutions of saccharin (0.02, 0.04, 0.20 and 2.0% w/v) or water for 2 h each day. Rats were then treated with different doses of 8-OH-DPAT (10, 60 or 100 micrograms/kg) or gepirone (1 or 2.5 mg/kg) in a repeated measures design. Under saline injection an inverted-U shaped concentration-response curve was obtained, with the highest level of intake occurring in rats drinking from the 0.20% saccharin solution. The highest doses of 8-OH-DPAT and gepirone suppressed drinking of saccharin, particularly over the first 30 min of the test period, leading to a flattening of the concentration response curve. At 2 h post-injection 60 micrograms/kg 8-OH-DPAT enhanced the consumption of the 0.04% saccharin solution only. In a second experiment, 8-OH-DPAT or gepirone was administered to rats eating either standard pelleted chow or the same food presented in powdered form. Both drugs stimulated feeding. However, interactions with food type were found. At 60 and 100 micrograms/kg 8-OH-DPAT increased eating of both food types equally, but with 500 micrograms/kg rats are significantly more of the pelleted food.(ABSTRACT TRUNCATED AT 250 WORDS)

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

PubMed1991

Serotonin-depleting midbrain lesions do not prevent ovariectomy-induced weight gain.

Past research has shown that subdiaphragmatic vagotomy and midbrain raphe lesions are each effective in impeding the development of hypothalamic obesity while neither affects the development of genetic obesity in Zucker rats. To further test the parallels that may exist between these two manipulations on another putative obesity model, we studied the effects of midbrain raphe lesions on the development of ovariectomy-induced weight gain, previously shown to be unaffected by vagotomy. Ten adult female rats received thermal lesions of the dorsal and median raphe nuclei (RAPHE) while 7 served as sham controls (SHAM). Following a 26-day recovery period during which body weight, food intake and water intake were periodically monitored, bilateral ovariectomy (OVX) was performed on 7 RAPHEs and 4 SHAMs, with laparotomy (LAP) being performed on 3 RAPHEs and 3 SHAMs. Body weights and intake variables were monitored for an additional 58 days, then animals were sacrificed for brain histological and biochemical assessments. RAPHEs weighed less despite eating and drinking more than SHAMs throughout this study. Nevertheless, OVX rats gained more weight regardless of lesion (mean +/- SEM weight gain = 73.9 +/- 5.5 g for RAPHE + OVX and 67.0 +/- 6.6 g for SHAM + OVX vs. 30.7 +/- 3.0 g for RAPHE + LAP and 39.7 +/- 5.5 g for SHAM + LAP). This occurred without reliable changes in the food or water intakes of either OVX subgroup. Histology confirmed that RAPHE lesions were largely localized to the dorsal and median raphe nuclei, as planned.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Effects of systemic 8-OH-DPAT on the feeding induced by hypothalamic NE infusion.

Past research suggests that activating brain serotonin (5-hydroxytryptamine or 5-HT) systems can inhibit feeding induced by activating brain norepinephrine (NE) systems. To explore this interaction more fully, we tested the capacity of the endogenous 5-HT release inhibitor, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), to enhance feeding stimulated by infusing NE into the medial hypothalamus. All experiments were conducted using ad lib-fed adult male rats with indwelling cannulae aimed at the paraventricular nucleus (PVN). In the first study, proven PVN-NE responders were tested for 40-min food intake after receiving 20 nanomoles (nmol) 1-NE or saline in the PVN following subcutaneous (SC) pretreatment with 250 micrograms/kg 8-OH-DPAT or saline. Both drugs produced equivalent, reliable increments in feeding compared to PVN-saline. However, no additivity or synergy was seen when they were combined. Short-term water intake was unaffected by these treatments as was subsequent food or water intake over the next 22 hr. In a second study, additional proven PVN-NE responders were tested under two comparable conditions when 1) the 8-OH-DPAT dose was left at 250 micrograms/kg but the NE dose was lowered to 10 nmol, and 2) the 8-OH-DPAT dose was lowered to 120 micrograms/kg and the NE dose was increased to 40 nmol. In the first case, no reliable feeding was seen in response to either agent alone or combined. In the second case, NE alone enhanced feeding but 8-OH-DPAT did not. The combination of both produced the same enhanced feeding as seen with NE alone.(ABSTRACT TRUNCATED AT 250 WORDS)

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