Biomedical subjects

D V Coscina

Publications and source records attributed to D V Coscina.

At least 19 recordsLinked to original sources

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↗

PubMed1990

Regional changes in brain 14C-2-deoxyglucose uptake after feeding-inducing intrahypothalamic norepinephrine injections.

Although norepinephrine (NE) injections into the paraventricular hypothalamus (PVN) have been extensively documented to induce feeding in satiated rats, there have been few systematic attempts to elucidate the neural circuitry subserving this response. In this study quantitative 14C-2-deoxyglucose (14C-2DG) autoradiography was used to map regional brain changes induced by PVN NE injections. Male Wistar rats, bearing PVN cannulae and previously shown to be positive responders for NE-induced feeding, were given 125 microCi/kg 14C-2DG IV immediately following a PVN injection of either 40 nmol NE or vehicle, then killed 45 min later. 14C-2DG uptake was examined in 97 brain structures using computerized densitometry. PVN NE injections resulted in small, localized changes in brain 14C-2DG uptake. Forebrain structures affected included the somatosensory parietal cortex (+15%), the CA3 hippocampal field (-8%), and the reticular thalamic nucleus (+14%). Midbrain changes involved the anterior pretectal area (+8%) and the central gray area (-11%). At the hindbrain level, the lateral reticular nucleus showed the most pronounced changes of all brain regions examined (-24%), followed by the nucleus of the solitary tract (-16%) and the laterodorsal tegmental nucleus (+16%). No changes were seen in the median eminence or in other hypothalamic areas. This pattern of results largely agrees with recent proposals for the circuitry of a PVN-hindbrain system subserving NE-induced as well as hypothalamic lesion-induced feeding effects. In addition, however, they suggest the possibility that altered activity in some forebrain structures may also be involved in the NE response.

Animals↗

PubMed1990

Neonatal 6-hydroxydopamine alters the behavior of enriched-impoverished rats in a novel test environment.

The hypothesis that neonatal norepinephrine (NE) depletion lessens the behavioral consequences of differential housing was tested. Male Wistar rats were injected with 6-hydroxydopamine (6-OHDA) or vehicle twice within 24 hr of birth, weaned at 25 days, and reared under either impoverished (IC) or enriched conditions (EC) for 30 days. In 3 experiments, rats were tested in the Morris water maze, the colony-intruder test, and 2 tests of dominance. 6-OHDA treatment reduced cortical and hypothalamic NE concentrations and increased brainstem NE concentrations. EC housing increased cortical dopamine (DA). Behavioral differences caused by postweaning enrichment-isolation were reduced by neonatal NE depletion, primarily in early test trials. The authors conclude that forebrain NE afferents from the locus coeruleus are important for housing-related behavioral changes and responsivity to novel testing environments.

Agonistic Behavior↗

PubMed1989

Effects of lateral hypothalamic lesions on the anorexia induced by ethanolamine-O-sulfate.

Intracisternal (IC) injection of the GABA-transaminase inhibitor, ethanolamine-O-sulfate (EOS), has been previously shown to induce dose-dependent anorexia in normal rats as well as to reverse overeating in several rodent models of acute and chronic hyperphagia. To determine if such anorexia might be mediated by cells within or fibers of passage which traverse the lateral hypothalamus (LH), adult female rats received bilateral radiofrequency heat lesions of the LH vs. anesthesia control injections and were allowed to recover normal feeding and drinking responses. Using a longitudinal design, all animals then received 100, 0, and 200 micrograms EOS in 20 microliters deionized water IC with 1 week separating each injection. In addition to daily measures of feeding, drinking and body weight, all animals were screened 24 hr after injections for sensorimotor competence and general health by testing open-field activity, catalepsy, paw-lick responses on a hot-plate and rectal temperature. As reported previously, IC EOS induced dose-dependent hypophagia and weight loss. However, the magnitude and duration of these effects were equivalent in lesioned and control rats. In addition, open-field activity and body temperature were reliably lowered as a function of dosage while catalepsy was increased. Again, this effect was equivalent in lesioned and control rats. Subsequent tests of drinking and feeding in response to hyperosmotic and hypoglycemic challenges, respectively, confirmed that lesioned rats were deficient compared to controls. These findings suggest that an intact LH axis is not required for the anorexigenic effects of IC EOS.

4-Aminobutyrate Transaminase↗

PubMed1989

Intake of greasy diets in hypothalamic obesity: a re-assessment.

Rats with medial hypothalamic lesions are known to prefer greasy diets. Past research has suggested that this is based on the oily texture rather than caloric content of these foods. We have re-examined this appetite in rats with bilateral parasagittal knife-cuts between the medial and lateral hypothalamus. Following knife cuts vs. sham surgery, the body weight and food consumption of adult female rats were monitored during four experimental phases. During the first month post-surgery rats were fed powdered Chow (3.61 kcal/g) and showed the usual hyperphagia and obesity. Each group was then subdivided and fed either a high-fat diet (5.5 kcal/g) or a similarly greasy mineral-oil diet (3.61 kcal/g) for a second month. The knife-cut group fed high-fat showed significantly higher intake than both sham-cut controls and knife-cut rats fed the mineral-oil diet. The latter group showed only a non-significant feeding increase over controls. Following a third month when all groups again received Chow, animals were given the opposite greasy diet for a final month. Knife-cut rats previously fed the high-fat diet showed significant overeating of the mineral-oil diet and defended their obesity, while those fed the mineral-oil free diet first now showed significant hyperphagia and obesity on the high-fat diet. Across both target phases (months 2 and 4) knife-cut rats always ate significantly more of the high-fat diet than of the mineral-oil diet. The latter only elicited hyperphagia in animals that had been previously exposed to the high-fat diet. These findings suggest that the hyperphagic response to greasy foods relatively low in calories and digestible fats by rats with hypothalamic injury is a function of prior experience with the sensory and/or metabolic consequences of having first eaten highly caloric fatty foods. If that is true, it may be that such animals are capable of learning positive food-associated cues in addition to negative ones (i.e. enhanced taste aversions) documented earlier by other investigators.

Animals↗

PubMed1988

Graded increases in brain GABA: differential effects on feeding and other behaviours in rats.

Elevations of brain gamma-aminobutyric acid (GABA) induced by inhibitors of GABA transaminase (GABA-T) are known to induce a number of functional effects including depression of food intake. The aim of the present study was to determine the brain GABA elevation threshold for changes in feeding and several other behaviours, in an effort to clarify whether feeding changes might be secondary to other functional deficits. To this end, various doses of the GABA-T inhibitors ethanolamine-o-sulfate (EOS) and gamma-vinyl GABA (GVG) were injected intracisternally and effects on whole brain GABA, food and water intake, open field activity, catalepsy indices, pain sensitivity, and core temperature were assessed 24 h later. Progressive increases in brain GABA levels were found to differentially affect the responses studied. At the low end of the continuum, significant decreases in feeding behaviour were associated with relatively modest increases in brain GABA (40-60%). At higher levels of GABA elevation (greater than 100%), changes in motoric functions and rectal temperature became apparent. At still higher levels (greater than 200% increases in brain GABA), significant antinociceptive effects were detected. These results support the notion that feeding decreases induced by low doses of GABA-T inhibitors may reflect a fairly specific effect on appetite mechanisms, but also indicate that with increasingly higher doses several other deficits are likely to contribute to the overall decrease in food intake.

4-Aminobutyrate Transaminase↗

PubMed1988

Lateral and medial hypothalamic lesions do not acutely affect brown adipose tissue thermogenesis.

The acute effect of lateral (LH) and medial (MH) hypothalamic lesions on mitochondrial GDP binding in brown adipose tissue (BAT) (an index of thermogenic state) was studied one and two days postlesion. Groups of rats were lesioned, sham-lesioned, or unoperated and were all fasting. An additional group of unoperated rats had access to food throughout the study. The objective was to determine whether the hypermetabolic state and rapid weight loss known to be induced by LH lesions were attributable to the activation of BAT thermogenesis, and, if so, whether these effects were specific for LH lesions. No effect of either lesion on BAT thermogenic state could be detected at either time studied. Despite that fact, LH-lesioned rats, but not MH-lesioned rats, were hyperthermic at both times. We conclude that the prolonged hyperthermia which occurs shortly after LH lesions is not due to an activation of BAT thermogenesis. Instead, it can be likened to the febrile state in which an initial and brief activation of both nonshivering thermogenesis in BAT and shivering thermogenesis in muscles occurs only during the rising phase of the fever and is suppressed as soon as a stable hyperthermic state is reached. It thus appears unlikely that substantial and prolonged activation of BAT thermogenesis is a major mechanism that promotes exaggerated short-term weight loss in the LH-lesioned rat.

Adipose Tissue, Brown↗

PubMed1986

Dopamine-norepinephrine interactions in the development of hyperphagia and obesity following medial hypothalamic lesions.

Conflicting evidence exists on the ability of central 6-hydroxydopamine (6-OHDA) injections to alter the subsequent development of hyperphagia and obesity following medial hypothalamic lesions (MHL) in rats. An initial study found no effects of prior intracisternal (IC) 6-OHDA on the subsequent development of this MHL syndrome, while later work reported that a dopamine (DA) depletions induced by intracerebral 6-OHDA effectively blocked it. The present study reexamined this issue by investigating the effects of depleting brain dopamine, norepinephrine (NE), or both DA and NE, on overeating and obesity induced by subsequent MH lesions. Different patterns of DA and NE depletions were achieved by IC 6-OHDA in combination with systemic pretreatments designed to protect central NE, DA, or neither amine, respectively. It was found that 6-OHDA regimens that selectively depleted forebrain DA did prevent the development of hyperphagia and obesity following MHL. However, when such forebrain DA depletions were accompanied by NE depletions no such blockade occurred. Manipulations which selectively depleted forebrain NE had no effect on MHL-induced hyperphagia and obesity. These results offer a framework for resolving previous discrepancies in the literature concerning brain monoamines and MHL effects. They also indicate that the effectiveness of brain DA depletions in blocking the MHL syndrome is critically dependent on the functional status of NE systems.

Animals↗

PubMed1979