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H J Grill

Publications and source records attributed to H J Grill.

At least 73 records · Page 4Linked to original sources
PubMed1990

Conditioned reversal of reactions to normally avoided tastes.

Oral motor responses, elicited by the infusion of a taste solution into a rat's mouth, can be changed through association with either other tastes or internal states. Such changes have been well established when ingestive responses, elicited by a normally preferred taste, are changed to aversive responses when the taste signals a LiCl injection. However, the converse has yet to be clearly established; that aversive responses, elicited by a normally avoided taste, can be changed to ingestive responses in a nondeprived animal, as a result of conditioning. We demonstrate here that when a normally avoided taste (quinine or HCl) signals a preferred taste (sucrose), the oral motor responses gradually undergo two types of change as a function of trials. The aversive oral motor responses elicited by the avoided taste decrease over trials and the ingestive responses increase. The two measures, ingestive and aversive responding, were obtained by recording the rat's reactions to the stimuli as they were infused directly into the oral cavity. This taste reactivity method both enabled us to use avoided stimuli in a nondeprived animal and to measure the rat's evaluation of the stimuli's aversiveness. Problems with stimulus sampling may be responsible for the dearth of conditioning experiments which utilize avoided tastes in conditioned preference studies.

Animals↗
PubMed1990

Lack of binding of gestodene to estrogen receptor in human breast cancer tissue.

Competition studies with progesterone and estradiol receptors of human myometrial tissue as well as of mammary cancer tissue showed that gestodene bound with high affinity to the progesterone receptor, as did other synthetic and natural progestogens. However, gestodene did not bind to the estradiol receptor. The relative binding affinities of all tested synthetic and natural ligands showed no organ-specific differences and no differences between neoplastically transformed and normal tissues.

Binding, Competitive↗
PubMed1990

Ingestion rate as an independent variable in the behavioral analysis of satiation.

A novel intake testing paradigm, allowing explicit adjustment of the rate of sucrose ingestion via intraoral delivery, was used to investigate the effects of ingestion rate on ingestion duration and amount consumed. In experiment I, 12 rats were tested under each of three sucrose concentrations (0.1, 0.3, and 1.0 M) delivered at each of four rates (0.5, 1.0, 1.5, and 2.0 ml/min). For each stimulus concentration, intraoral intake varied as a decreasing linear function of ingestion rate (infusion rate). In experiment II, a second (part B) infusion (0.5, 1.0, or 1.5 ml/min) was initiated 30 s after an initial (part A) infusion (0.5, 1.0, or 1.5 ml/min) of the same stimulus was rejected. Amount consumed during the part B infusion was substantial only when the part B infusion rate was lower than that of part A. Quantitative analysis of experiment II indicated that across sessions with common part B infusion rates, total session intake remained stable regardless of 1) whether the part A ingestion rate was greater than or equal to that of part B, 2) systematic differences in part A intake and duration, 3) differences in total session duration, and 4) differences in average ingestion rate for the session (total session intake/total session duration). The behavioral results are discussed in relation to the analysis of satiety under traditional intake testing paradigms and to gastric and postgastric theories of satiety.

Analysis of Variance↗
PubMed1990

Chemospecific deficits in taste detection after selective gustatory deafferentation in rats.

Electrophysiological data support the existence of sodium-specific taste receptors that appear to be limited to the anterior tongue. However, previous behavioral findings suggest that bilateral transection of the chorda tympani nerve (CTn) has minimal consequences on NaCl intake and preference. This study employed a conditioned avoidance procedure to measure detection thresholds to NaCl and sucrose both before and after bilateral transection of the CTn. Rats were trained to maintain spout contact in response to water presentations (70 microliters) and to avoid spout contact when a taste solution (70 microliters) was presented. In experiment 1, all rats (n = 3) showed statistically significant impairments in the detectability of NaCl after bilateral section of the CTn. The mean increase in the NaCl detection threshold was 1.41 log units. In contrast, sucrose threshold in these same rats was marginally affected by CTn section (mean increase = 0.22 log units). Experiment 2 (n = 4) replicated the findings of the first experiment. The mean increase in the NaCl detection threshold was 2.23 log units. Sucrose threshold in these rats was, again, only marginally affected by CTn section (mean increase = 0.83 log units). Histological examination of the anterior tongue from the rats in experiment 2 indicated that the CTn transections were complete. These findings reveal that the anterior oral receptive field (innervated by the CTn) containing only 15% of the total taste bud population is critical for the normal detection of NaCl.

Afferent Pathways↗
PubMed1990

[Steroid hormone receptor status of colorectal cancers].

Tumor samples of 26 consecutive colorectal carcinomas were studied for the presence of steroid hormone receptors for estrogen and progesterone. In all cases, the estradiol receptor binding capacity was below 2 fmol/mg cytosol protein. In 4 of 26 samples, progesterone receptor levels from 13 to 23 fmol/mg cytosol protein were observed. Because of the identification of steroid receptors in some cases and single reports in literature about tumor regression under hormone therapy of colorectal carcinoma, further investigations seem indicated to study the hormone sensitivity of colorectal carcinoma.

Aged↗
PubMed1989

Swallowing during ongoing fluid ingestion in the rat.

In order to identify fixed versus flexible aspects of swallowing and oromotor control, we developed a method for the concurrent analysis of swallow frequency, swallow volume, and the temporal correlation between swallowing and rhythmic orolingual movements during prolonged bouts of fluid ingestion in unanesthetized, unrestrained rats. Rats actively ingested 0.1 M sucrose solutions infused intraorally: (a) at a constant rate within sessions; and (b) during separate sessions across which the rate of intraoral infusion (= ingestion rate) was varied. Salient characteristics of 'intraoral intake' included: (1) covariation of swallow frequency and swallow volume to mediate adjustments in the rate of ingestion; (2) emission of rhythmic coupled movements (5-7 Hz) of the jaw and tongue that serve to transport fluid through the mouth; (3) a 20-40 ms increase in the duration of the rhythmic movement cycle associated with swallow onset; and (4) emergence of pauses between bursts of rhythmic oromotor behavior with increases in cumulative intake. That intraoral intake and fluid ingestion via spout-licking (Weijnen et al., Brain Behav. Evol., 25, 1985) share all of these features suggests strongly that common neural processes, relatively uninfluenced by sources of sensory feedback attending contact with an environmental fluid source, underlie these aspects of normal fluid ingestion. The dynamic adjustment of swallow frequency and swallow volume presents a challenge to traditional models of reflexive swallow initiation derived primarily from the neurophysiological study of acute, non-behaving preparations.

Animals↗
PubMed1989

3H-ZK 98,734, a new 11 beta-aryl substituted antigestagen: binding characteristics to receptor and serum proteins.

Recently, in the laboratories of Schering in Germany a competitive progesterone antagonist, ZK 98,734, was synthetized, which is characterized by a similar antigestagenic activity as RU 38,486, synthezised by Roussel-Uclaf in France, as assessed by inhibition of nidation tests in rats and guinea pigs. However, this compound has a substantially lower antiglucocorticoid activity measured in cell culture systems than RU 38,486. The purpose of this study was to present a comparison of biochemical and physical properties of the complexes formed by the human uterine progesterone receptor with 3H-ZK 98,734 on one hand and with other well-established progestins on the other hand. ZK 98,734 competed in the same order of magnitude as progesterone or RU 38,486 for the 3H-R5020 binding site of progestin receptor, whereas R5020, Org 2058 or progesterone were unable to compete against 3H-ZK 98,734. This apparent contradiction could be explained by means of FPLC-chromatography and sucrose density centrifugation technique. FPLC-chromatography with an anion exchange column (Mono Q, Pharmacia, Uppsala, Sweden) showed that 3H-ZK 98,734 forms at least two stable complexes with uterine cytosol, on one hand with serum albumin, which presents almost 90% of bound radioactivity, and on the other hand with the two native progestin receptor forms, corresponding to 4S and 8S receptor forms in sucrose density gradient analysis. Competition experiments in liver cytosol of adrenalectomized rats with increasing concentrations of unlabeled ligands other than dexamethasone showed that ZK 98,734, RU 38,486 and cortisol displaced 3H-dexamethasone efficiently from the binding sites in the cytosol. Furthermore, results concerning the specificity of 3H-cortisol binding to serum proteins in diluted pregnant serum demonstrated that ZK 98,734 did not compete with 3H-cortisol for serum binding.

Animals↗
PubMed1989

Gestodene: a novel synthetic progestin--characterization of binding to receptor and serum proteins.

Gestodene, 17 alpha-ethinyl-13-ethyl-17 beta-hydroxy-4,15-gonadien-3-one, is a new orally active progestational agent, which is available for clinical use in oral contraceptives. The aim of the present study is to make a broad characterization of gestodene at the receptor level and to discuss the results in comparison to those of established progestogens. Kinetic studies of 3H-gestodene uptake show a rapid increase in the amount of specific binding during the first three hours. After saturation, the amount of specifically bound 3H-gestodene remained almost constant up to 24 hours at 4 degrees C. The dissociation of 3H-gestodene from the cytoplasmic myometrial progestone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a biphasic or two-component first order dissociation curve. As anticipated, sucrose gradient centrifugation analysis of the 3H-gestodene-labeled cytosol of human myometrial tissue showed that the gestodene binding components sedimented in the 4S and 8S region. A 200-fold molar excess of nonradioactive gestodene reduced only the 8S binding of 3H-gestodene. 4S binding of 3H-gestodene was not reduced, which indicate the existence of a second high capacity binding component. In biological test systems, such as the Clauberg test or Kaufmann test, gestodene has proved to be a very effective progestogen. Among nortestosterone derivatives it is one of the most potent and resembles progesterone biologically in its progestogenic effects. This biologically identical gestagenic activity of gestodene and progesterone is reflected by a very similar behavior in vitro in terms of binding to progesterone receptors of human uterus cytosol. Furthermore, competitive studies indicated that gestodene like other synthetic progestagens also displays some affinity for androgen and glucocorticoid receptors but no measurable affinity for the estrogen receptor. Remarkable is the high binding affinity of gestodene to the binding sites of the mineralocorticoid receptor of rat kidney with a RBA value of 350% compared to aldosterone.

Animals↗
PubMed1988

Contribution of fat metabolism to 'glucoprivic' feeding produced by fourth ventricular 5-thio-D-glucose.

We examined whether manipulations of fat metabolism influence the feeding response to peripheral or central administration of 5-thio-D-glucose (5-TG), a potent inhibitor of glucose utilization. The increase in food intake produced by peritoneal (50 mg/kg) or fourth ventricular (50, 100, 150 micrograms) 5-TG was potentiated by administration of the fatty acid oxidation inhibitor, methyl palmoxirate (10 mg/kg, p.o.). In addition, rats maintained on a high-fat diet ate less in response to fourth ventricular 5-TG (150 micrograms) than did rats maintained on an equicaloric low-fat diet. These results suggest that the feeding response to 'glucoprivation' is determined by the interaction of glucose and fat oxidation.

Animals↗
PubMed1988

Taste responses in the nucleus tractus solitarius of the chronic decerebrate rat.

The ingestive behavior of decerebrate rats has been studied for some time, yet little is known of its neural substrates. While taste fibers in rats proceed from hindbrain to thalamus and ventral forebrain, these regions return centrifugal fibers to the hindbrain by which lower-order taste activity may be influenced. We examined the functional characteristics of taste neurons in the nucleus tractus solitarii (NTS) of chronic decerebrate rats in which this reciprocal communication was disrupted and compared them with those of intact controls. Nine Wistar rats were decerebrated at the supracollicular level. After a minimum of one week recovery, they were immobilized with Flaxedil, anesthetized locally and prepared for recording. The responses of 50 taste cells were isolated bilaterally from the NTS of these animals, while the activity of 50 additional neurons was recorded from 12 intact rats under the same conditions. Taste stimuli included 7 Na-Li salts, 3 sugars, HCl and citric acids, quinine HCl and NaSaccharin. Mean spontaneous activity in decerebrates was 6.5 spikes/s, 36.0% lower than the level in intact animals. Mean evoked activity was reduced by 32.6%. Analyses of the effects of stimulus quality, intensity and time course of the responses all indicated that the decrease in activity was attributable to the inability of taste cells in decerebrate rats to respond to demands for high discharge rates. This deficit could be responsible for the failure of these animals to develop conditioned taste aversions. Neurons from decerebrate preparations did, however, retain the broad sensitivity across stimuli that characterized taste cells in intact preparations. It was also typical that most neuron response profiles from decerebrates could be grouped into 3 loose clusters with peak sensitivities to acid-salt, salt or sugar. An analysis of similarities among stimulus activity profiles indicated that Na-Li salts, sugars and an acid-quinine complex represented 3 groups of stimulus quality; in intact animals, the primary distinction was between sweet and non-sweet stimuli. Moreover, the response to sodium saccharin lost its bitter component in decerebrates. These findings were in general agreement with those derived from acute decerebrate rats.

Animals↗
PubMed1988

Comparison of the interoceptive sensory consequences of CCK, LiCl, and satiety in rats.

In three experiments we assessed the degree to which ad lib feeding, injection of cholecystokinin (CCK), and injection of lithium chloride (LiCl) produce states with similar sensory consequences. In each experiment, two groups of rats were trained to use cues arising from food deprivation and satiation as discriminative signals for shock. One group was shocked when deprived but not when nondeprived. The other group received the reversed discrimination. Testing began when incidence of freezing was greater under the shocked deprivation than under the nonshocked deprivation condition. In Experiment 1, the rats were tested under 24-hr food deprivation after injections of CCK, LiCl, and saline (in counterbalanced order). We reasoned that if either CCK or LiCl induce satiety-like states, they should promote patterns of responding different from those produced by saline but similar to those produced by ad lib feeding. The effects of CCK on freezing did not differ from those of saline, whereas both CCK and LiCl had effects that were different from ad lib feeding. This pattern of results was also obtained when deprivation level during training and testing was reduced to 8 hr (Experiment 1A) and also when rats received small amounts of food in conjunction with CCK (Experiment 2). The intubation of a high-calorie stomach load (Experiment 1A) produced a response profile like that observed after free feeding. Freezing after LiCl treatment differed from that observed after free feeding and from that found after injection of CCK. The results indicate that rats can differentiate between the sensory consequences of the states produced by CCK, by LiCl, and by ad lib feeding.

Animals↗
PubMed1988

Intraoral intake and taste reactivity responses elicited by sucrose and sodium chloride in chronic decerebrate rats.

The oral stimulating effects of sucrose and sodium chloride (NaCl) were assessed in chronic decerebrate and pair-fed intact control rats by measuring both oral motor taste-reactivity responses and intraoral intake volume. Taste-reactivity responses were videotaped during the first minute of the intraoral taste infusion. The infusion continued until the taste solution was rejected from the mouth, and the intake volume was computed accordingly. The number of ingestive taste-reactivity responses and the volume of intraoral intake consumed by pair-fed control and decerebrate rats increased with increasing sucrose concentration. Sucrose intake increased as concentration increased to 0.1 M, then plateaued between 0.3, 1.3, and 2.0 M sucrose for both groups. For control rats, intraoral NaCl elicited an inverted U-shaped function for both taste-reactivity responses and intake. Taste-reactivity responses of chronic decerebrate rats varied with NaCl concentration. In contrast to control rats, intake of NaCl did not differ from that of water for decerebrate rats. These data indicate that caudal brain-stem mechanisms are sufficient to control sucrose intake but are not adequate for the concentration dependent intake of NaCl. Second, these data also indicate that it is possible for taste-elicited oral motor responses to be dissociated from intake. The different roles of taste and postingestive factors in sucrose and NaCl intake are discussed.

Animals↗
PubMed1988

Taste reactivity as a dependent measure of the rapid formation of conditioned taste aversion: a tool for the neural analysis of taste-visceral associations.

Several explanations may account for deficits in the ability of animals to form taste aversions following neural manipulations. These encompass impairments in conditioned stimulus (CS) and unconditioned stimulus (US) processing, conditioned response (CR) measurement, and expression, memory, and taste-visceral integration. A behavioral procedure that aids in the distinction between some of these possibilities is presented. In Experiment 1, 10 rats received seven intraoral (IO) infusions of sucrose (30 s, 0.55 ml) spaced every 5 min starting immediately after the injection of 3.0 mEq/kg of lithium chloride (LiCl). Control rats (n = 12) were treated identically except that they were injected with sodium chloride (NaCl). Oromotor and somatic taste reactivity behaviors were videotaped and analyzed. Lithium-injected rats systematically decreased their ingestive taste reactivity behavior over time, whereas aversive behavior increased. Control rats maintained high and stable levels of ingestive responding and demonstrated virtually no aversive behavior over the 30-min period following sodium injection. Rats were tested several days later for the presence of a conditioned taste aversion (CTA). Rats previously injected with lithium during sucrose infusions demonstrated significantly more aversive behavior than the control group, which demonstrated none. There were no differences in the level of ingestive behavior displayed by the two groups on the CTA test. Experiment 3 revealed that when similarly treated rats were tested for a CTA while in a lithium-induced state, a difference in the ingestive behavior between the two groups was observed. In Experiment 2, naive rats were injected with either NaCl or LiCl but did not receive their first sucrose infusion until 20 min later. These rats also received sucrose infusions at 25 and 30 min postinjection. There were no differences in the taste reactivity behavior displayed by lithium- or sodium-injected rats during any of the sucrose infusions. Collectively, these findings indicate that rats dramatically change their oromotor responses to sucrose during the period following LiCl administration, provided that the infusions start immediately after injection. Furthermore, this time-related behavioral change is predominantly attributable to associative processes. This paradigm can be useful in distinguishing between neural manipulations that affect the establishment of taste-visceral associations from others that affect the animal's ability to retain such associations over the commonly employed 24-hr conditioning-test interval.

Afferent Pathways↗
PubMed1988

Effects of concentration presentation order and intraoral delivery on sucrose intake.

In this article, intraoral intake of an ascending concentration series of sucrose was found to plateau between concentrations of 0.3 M and 2.0 M, and thus failed to show the typical inverted U-shaped intake function found in standard intake tests. Two experiments were conducted to explain this result. In Experiment 1, intraoral and standard 30-min, 1-bottle intake of ascending sucrose concentrations (0.03, 0.1, 0.3, 1.0, 1.3, and 2.0 M) were compared. Sucrose intake was similar for both delivery methods. In a second experiment we examined the effect of the order of sucrose concentration presentation on the 1-bottle 30-min intake of nondeprived intact rats. An ascending concentration order of the solutions produced a significantly greater intake of concentrated sucrose solutions than did a random order. This result strongly suggests that the standard decline in sucrose intake at higher concentrations is determined not only by postoral factors but also by experiential factors (i.e., order of presentation).

Animals↗
PubMed1988

Cholecystokinin decreases sucrose intake in chronic decerebrate rats.

The capacity of chronic decerebrate rats to reduce their intake of an orally infused sucrose solution in response to peripherally administered cholecystokinin octapeptide (CCK-8) was investigated. The sucrose intake of both 24-h food-deprived chronic decerebrate rats and pair-fed control rats was reduced by CCK-8 relative to the intake after desulfated CCK-8. The intake-reducing effect of CCK-8 in the chronic decerebrate rat provides compelling evidence that the caudal brain stem is of sufficient neural complexity to mediate this response. Although others have hypothesized that connections between the caudal brain stem and forebrain are required to mediate this effect(s) of CCK-8, our results demonstrate that these pathways are not necessary.

Animals↗
PubMed1988

Strain differences in taste reactivity to NaCl.

The taste reactivity test was used to determine whether strain differences in response to NaCl revealed by preference tests were attributable to taste or postoral factors. Taste reactivity data revealed significant differences between sodium-replete Fischer 344 (F-344) and Wistar strains in response to NaCl for both aversive and ingestive oral motor behaviors. Because the taste reactivity test analyzed the immediate response to orally applied chemical stimuli, these data support a strain difference based on taste factors. Taste reactivity data also indicate strain differences in ingestive but not aversive scores to other normally ingested chemical stimuli, water, and two sucrose concentrations. In response to normally avoided quinine, F-344 and Wistar strains did not differ in either ingestive or aversive score. To investigate whether strain differences revealed when rats were tested while sodium replete would persist in the sodium-deficient state, both strains were treated with the diuretic furosemide. Taste reactivity tests revealed that in response to sodium deficiency both F-344 and Wistar strains shift their oral motor response profile to NaCl; strains did not differ in either ingestive or aversive score when sodium deficient. NaCl intake and preference measures also support the fact that both strains demonstrate a sodium appetite. Interpretive limitations based on ceiling and floor effects within taste reactivity and preference data were discussed.

Animals↗
PubMed1987

Application of liquid-liquid partition chromatography in the simultaneous purification of sex-hormone-binding globulin and corticosteroid-binding globulin.

Two human serum proteins, corticosteroid-binding globulin (CBG) and sex-hormone-binding globulin (SHBG), were purified to homogeneity by the application of a combination of three different modes of chromatography. Human pregnancy serum was fractionated with ammonium sulphate. SHBG (50% pellet) and CBG (80% pellet) were then purified by affinity chromatography on tresyl-activated Sepharose with 15-aminopentadecanoic acid (for SHBG) and 1,12-diaminododecane (for CBG) as spacers and 17 zeta-aminoethyl-5 alpha-androstan-3 beta,17-diol (for SHBG) and 17 alpha-hydroxy-4-androsten-3-one-17 beta-carboxylic acid (for CBG) as specific ligands for these two proteins. The eluate was injected into a Mono Q anion-exchange column. Fractions containing SHBG or CBG were finally purified by liquid-liquid chromatography on Lipar-Gel 750. This chromatographic sequence clearly separated SHBG and CBG from other proteins, mainly serum albumin, without a loss of protein or binding activity.

Chromatography, Affinity↗