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D V Coscina

Publications and source records attributed to D V Coscina.

At least 19 recordsLinked to original sources

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

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

Effects of central 5,7-dihydroxytryptamine on the medical hypothalamic syndrome in rats.

The present study attempted to replicate and extend two recent studies that implicated aberrant brain 5-HT neurotransmission in the etiology of overeating and BW grain. Adult female rats received 25 mg/kg of desipramine hydrochloride 30--45 min prior to an intracisternal injection of 200 microgram (free base) of 5,7-DHT creatinine sulfate or its 1% ascorbic acid aqueous vehicle. After 7 weeks of measuring food intake, water intake, and BW change, rats from both groups received radiofrequency lesions of the MH or sham surgery. After 5 additional weeks of intake and BW measurements, all rats were tested for 24-hr acceptance of varying sucrose and quinine solutions and for 25-day acceptance of a high-fat replacement diet. While 5,7-DHT depleted brain 5-HT by 45%, it did not induce overeating and BW gain alone nor did it modify the overeating, obesity, or "finickiness" produced by hypothalamic injury. Several factors that relate to specificity, sufficiency, and compatibility with other 5-HT depletory techniques were discussed, as were factors of similarity and dissimilarity between this and the previous experiments that we attempted to replicate.

5,7-Dihydroxytryptamine

Association of altered brain norephinephrine and serotonin with the obesity induced by goldthioglucose in mice.

Two experiments examined the possibility that mice rendered obese by systemic injection of goldthioglucose (GTG) possess altered endogenous levels of brain norepinephrine (NE), dopamine (DA), serotonin (5-hydroxytryptamine or 5HT) and/or 5-hydroxyindoleacetic acid (5HIAA). In the first experiment, single-housed GTG-obese mice were found to have normal brain DA and 5HIAA but 14% less NE and 6% less 5HT than controls. This neurochemical profile was strikingly similar to that previously reported for rats rendered obese by ventromedial hypothalamic lesions (i.e., normal DA and 5HIAA, 19% less NE, 7% less 5HT). However, in the second experiment, equally obese GTG mice pair-housed with non-obese controls showed normal DA, 5HIAA, and NE but 9% more 5HT than controls. In other words, absolute levels of these brain substances were inconsistent with respect to obesity across experiments. On the other hand, when ratios of all possible combinations of these compounds were compared across experiments, only 5HT/NE ratios were consistently different (higher) in GTG mice. In addition, reliable inverse correlations were obtained between weight gain parameters and brain 5HT/NE or 5HIAA/NE ratios for GTG mice. These findings suggest that interactions between brain 5HT and NE neurons may contribute to the overeating and obesity which occur in mice after GTG administration.

Animals

Body awareness in anorexia nervosa: disturbances in "body image" and "satiety".

Patients with anorexia nervosa have been shown previously to display distortions in body image perception. Bruch has postulated that these disturbances as well as disturbances in interoception are meaningfully related to the development of the syndrome. We hypothesized that disturbances in body image, as measured by a distorting photograph technique, and interoception, as measured by a satiety-aversion to sucrose test, should be demonstrable in anorexic patients vs. normal controls. Furthermore, these disturbances should be modifiable by external cues (looking at one's image in a mirror and ingesting isocaloric "high" and "low" calorie connotation meals). We also hypothesized that body image and interoceptive disturbances would be interrelated in the same individuals. Results indicated that patients with anorexia nervosa (N = 26) differed from normal controls (N = 16) in overestimating their body sizes (p = 0.06) and in failing to develop an aversion to the sucrose tastes (p less than 0.001). However, neither viewing one's image in a mirror nor ingesting both "high and "low" calorie connotation meals altered body size perception. Intrasubject body size estimates were very stable from week to week for the anorexic subjects (r = +0.75, p less than 0.001) but less for the controls (r = +0.45, p less than 0.05). The data revealed that overestimation of body size was closely related to the failure to develop an aversion to sucrose tastes in anorexic patients.

Adult

Selective blockade of hypothalamic hyperphagia and obesity in rats by serotonin-depleting midbrain lesions.

Adult female rats, depleted of 70 percent of forebrain serotonin by dorsal and median raphe lesions, showed little overeating of food pellets and obesity following medial hypothalamic lesions. However, these rats showed the same reduced acceptance of sucrose solutions, enhanced rejection of quinine solutions, and exaggerated weight gain on a high-fat diet as did other rats made obese by medial hypothalamic lesions alone. Since raphe lesions alone produced none of these effects, the pattern of behaviors observed suggests a hitherto unknown (perhaps secondary) role for brain serotonin metabolism in selective aspects of the medial hypothalamic syndrome.

Animals

Taming effects of handling on 6-hydroxydopamine induced ratge.

The purpose of this experiment was to determine the importance of handling to the expression of hyperemotional behaviors, i.e., rage, known to occur after chronic depletion of brain norepinephrine (NE) and dopamine (DA) following central injection of 6-hydroxydopamine (6-OHDA) in rats. Five min of handling per day for 6 consecutive days reduced resistane to capture as well as the magnitude and frequency of startle responding following one 300 mug injection of 6-OHDA intracisternally. Both 6-OHDA-handled and 6-OHDA-unhandled rats showed comparable levels of brain NE, DA, serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), comparable resting levels of plasma corticosterone, and comparable adrenal weights. These data demonstrate the importance of handling to the expression of 6-OHDA-induced rage and emphasize the importance of controlling for handling as a variable which can significantly affect the assessment of rage by behavioral criteria in this animal model of hyperemotionality.

Anger

Effect of midbrain raphé lesions or intracisternal 6-hydroxydopamine administration on D, L-5-hydroxytryptophan-14C metabolism after peripheral decarboxylase inhibition.

Brain and blood 14C-5-hydroxyindole metabolism was studied in normal, raphé-lesioned and 6-hydroxydopamine (60HDA)-treated rats given L-(-)-alpha-hydrazino-3, 4-dihydroxy-alpha-methylhydrocinnamic acid (MK-486) (50 mg/kg) intraperitoneally and 5-hydroxytryptophan (5-HTP)-14C (5 muCi, 0.51 mCi/mmol) intravenously. Raphé lesioning and 60HDA treatment caused significant decrements in brain 5-hydroxytryptamine (5-HT)-14C and 5-hydroxyindoleacetic acid (5-HIAA)-14C levels and 5-HT concentrations compared to those in normal controls. In normal and 60HDA-treated rats there were decreased brain dopamine levels, possibly a consequence of non-specific metabolism of 5-HTP in brain. Blood 5-HIAA-14C levels were significantly decreased in 60HDA-treated but not raphé-lesioned rats. As increased brain 5-HT turnover was observed in raphé-lesioned rats, this may have prevented a decrease in blood 5-HIAA-14C levels. The results suggest that changes in blood 5-HIAA-14C following MK-486 and 5-HTP-14C may be related to changes in brain 5-HT-14C metabolism.

5-Hydroxytryptophan

Determination of picogram levels of brain serotonin by a simplified liquid chromatographic electrochemical detection assay.

A simplified assay is described for measurement of picogram amounts of serotonin (5-HT) by high pressure liquid chromatography with electrochemical detection (LCEC). The procedure involves pre-purification of brain 5-HT by adsorption on Amberlite CG-50. Serotonin is subsequently resolved and detected by LCEC on Zipax SCX resin. The present method gives working sensitivities of at least 100 pg, tissue recoveries of 95% and very low interassay variability (coefficient of variation = 3%). Determination of rat brain area 5-HT by this LCEC method is described and compared to other high sensitivity methods.

Animals