Biomedical subjects

H J Grill

Publications and source records attributed to H J Grill.

At least 55 records · Page 3Linked to original sources

PubMed1993

Lesions of the central nucleus of the amygdala. II: Effects on intraoral NaCl intake.

Bilateral lesions of the central nucleus of the amygdala (CeAX) disrupt both need-free and need-induced NaCl intake. Quite surprisingly, in response to sodium depletion, the same rats who fail to augment their NaCl consumption dramatically increase the numbers of oral motor behaviors associated with ingestion that they display when NaCl is presented intraorally. The present study attempts to resolve these apparently contradictory results by measuring the intake of a NaCl solution delivered directly into the mouth. Controls enhanced their intraoral intake of 0.5 M NaCl in response to sodium depletion while CeAX rats did not. CeAX rats, however, showed discriminative intake responses to tastes. Like controls, CeAX rats promptly rejected 0.3 mM quinine infusions and ingested 1.0 M sucrose for prolonged periods. In addition, food deprivation enhanced the intraoral intake of a dilute sucrose solution in both CeAX and control rats. Thus, in the CeAX rat some tastes and some internal states modulate intake as they do in intact rats. These results are consistent with the hypothesis that central nucleus of the amygdala damage interferes with the consummatory phase of NaCl intake behaviors.

Administration, Oral↗

PubMed1993

Effects of interrupting an intraoral meal on meal size and meal duration in rats.

Most experiments on satiation do not separate the contribution to meal size of cumulative intake from that of time since meal onset. To assess the relative contributions of temporal and intake factors, the amount consumed of intraorally infused 12.5% glucose solution, delivered at a fixed rate of 1.0 ml/min, was assessed after tests that were interrupted for variable durations (Experiments I and II) beginning at different times within the test meal (Experiment I). Rats' meal size did not vary despite the imposition of single or multiple pauses which interrupted ingestion for as long as 38 min. These results show that, within this paradigm, the duration of the meal varies in service of an intake "goal". Such a defense of meal size requires accurate monitoring of the postingestive load despite its redistribution by continued gastric emptying during the imposed pauses in ingestion.

Animals↗

PubMed1993

Concentration-dependent licking of sucrose and sodium chloride in rats with parabrachial gustatory lesions.

The medial zone of parabrachial nuclei (PBN) serves as an obligatory synapse in the central gustatory system in rodents. Lesions in the PBN impair taste aversion learning and depletion-induced sodium appetite in rats, and also alter the ingestion of sapid stimuli. Interpretation of these lesion-induced behavioral deficits requires an evaluation of whether taste function is compromised. The present study examined whether rats with PBN lesions could show normal concentration-dependent changes in licking behavior to very small volumes of NaCl and sucrose. Physiological state was also varied; taste responsivity was examined in water-deprived and nondeprived rats. In a specially designed gustometer, nine rats with electrophysiologically guided lesions in the PBN and five surgical controls were trained to lick a drinking spout to receive 10-s access to various concentrations of NaCl (0.03-1.0 M) and sucrose (0.01-1.0 M) during 30-min sessions. Water-deprived control rats progressively decreased their responses compared with water as the concentration of NaCl was raised. In contrast, water-deprived PBNX rats did not decrease their licking responses to NaCl relative to water until the concentration reached 1.0 M. In the nondeprived state, control and PBNX rats decreased their responsiveness as a function of NaCl concentration, and the two groups did not differ. The licking responses of water-deprived PBNX rats did not differ from control rats when sucrose was the stimulus. In the nondeprived condition, both groups monotonically increased their licking to sucrose as a function of concentration, but PBNX rats were significantly less responsive than controls.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Lick rate analysis of sodium taste-state combinations.

The combined effects of taste and physiological state on lick rate for NaCl were systematically evaluated in two experiments. In experiment 1 the lick rates of six groups of rats (Sprague-Dawley) were recorded during the first 3 min of a NaCl drinking bout, where each group received a different concentration. Half of the rats were depleted by injections of the diuretic-natriuretic furosemide (10 mg ip), whereas the other half were not. The inverted U-shaped concentration-response functions for sodium-replete rats peaked approximately at isotonicity. The replete lick rate function was uniformly elevated for rats examined in the sodium-depleted state. In experiment 2 each rat received access to all six solutions within a 40-min test session. Rats were tested twice, once in positive and once in negative sodium balance. The solutions were repeatedly presented in counterbalanced order in a series of 10-s exposures. The replete and deplete functions of the within-group study closely resembled those of the between-group study. When the deplete rats' function was divided into three segments coinciding with the beginning, middle, and end of the 40-min session, the functions were shifted down vertically but retained their shape. In general, sodium-state level dramatically affected the absolute lick rates but did not appear to shift the location of the concentration-response function along the horizontal (i.e., concentration) axis. The form of the function appears to have been determined by oral factors alone.

Analysis of Variance↗

PubMed1993

Chorda tympani section decreases the cation specificity of depletion-induced sodium appetite in rats.

Rats depleted of sodium by diuretic treatment were tested for their ability to respond selectively to NaCl after chorda tympani nerve (CTn) section (CTX). A variety of chloride salts (NaCl, KCl, NH4Cl, CaCl2) at two concentrations (0.05 and 0.3 M) were presented semirandomly to sodium-deplete rats in repeated single-stimulus trials (10 s). The responses of sodium-depleted surgical control rats (n = 8) were highly cation specific. These rats licked substantially more for both sodium stimuli than for any other chloride salt. On the other hand, the licking responses of CTX sodium-depleted rats (n = 8) were less cation selective. These rats licked NaCl and 0.05 M KCl at comparable rates. For both NaCl concentrations, CTX rats had significantly lower lick rates than controls. In addition, the difference between the lick rate for NaCl and that for the other salts was much greater for control rats than for CTX rats. Although CTn section did not entirely eliminate the high levels of responsivity to NaCl observed in the intact sodium-depleted rat, it did substantially compromise the selectivity of the behavior, which suggests that the input of the CTn is critical for taste-guided sodium specific behaviors.

Animals↗

PubMed1993

Daily caloric intake in intact and chronic decerebrate rats.

Daily caloric intake regulation was studied in chronic supracollicular decerebrate rats with a complete transection of the neural axis at the meso-diencephalic juncture and in intact controls. For 1 week, each rat received 3 intraorally delivered meals per day. They were challenged to maintain their 3-meal daily intake over 1 week in which only 2 meals per day were delivered. Intact rats increased meal size to compensate for the lost opportunity to feed, whereas chronic decerebrate rats did not. Results suggest that, although the caudal brainstem, as previously shown (Grill & Kaplan, 1990), is sufficient to modulate ingestive behavior in taste reactivity and single-meal tests, it is not sufficient to regulate daily caloric intake. Although it is possible that chronic decerebrate rats retain a long-term regulatory competence that is somehow masked under the meal omission paradigm, forebrain-hindbrain interactions appear necessary for the coordination of short- and long-term intake control processes.

Animals↗

PubMed1992

The contribution of gustatory nerve input to oral motor behavior and intake-based preference. I. Effects of chorda tympani or glossopharyngeal nerve section in the rat.

Two-bottle intake tests and taste reactivity (TR) tests were used to reveal whether changes in ingestive behavior would follow bilateral section of either the chorda tympani (CT) or the glossopharyngeal (GP) nerve. Rats received two-bottle intake tests to compare 24-h ingestion of water to that of NaCl, MgCl2, quinine, or sucrose. Prior to each long-term intake test, rats received a 1 min, 1 ml intraoral infusion of the same chemical stimulus. Ingestive and aversive oral motor responses elicited by these 1 ml infusions were videotaped and subsequently analyzed. GP-section did not alter quinine or sucrose preference; overall, preference of MgCl2 and NaCl was also similar to controls. In contrast, TR tests in GP-sectioned rats revealed that most quinine, MgCl2 and NaCl stimuli elicited significantly fewer aversive oral motor responses. In addition, the latency of aversive responses to these 3 chemical stimuli was increased for these rats. Intake-based preference tests failed to show any difference between rats with CT nerve section and controls. In TR tests, however, CT-sectioned rats displayed significantly fewer ingestive oral motor responses to NaCl, MgCl2, and quinine than controls. Neither sucrose intake nor sucrose-elicited TR were altered by CT or GP nerve section. This report confirms the failure of long-term intake tests to uncover behavioral deficits following the section of gustatory nerves. In contrast, the use of a different behavioral test makes clear for the first time that gustatory nerve section has dramatic consequences on ingestive behavior. The examination of taste elicited oral motor behaviors reveals a coherent and nerve specific pattern of neurological deficit following peripheral nerve section.

Animals↗

PubMed1992

The contribution of gustatory nerve input to oral motor behavior and intake-based preference. II. Effects of combined chorda tympani and glossopharyngeal nerve section in the rat.

Two-bottle preference and taste-elicited oral motor responses were examined to determine whether the total lingual gustatory denervation that results from combined bilateral chorda tympani (CTX) and glossopharyngeal nerve section (GPX) would (a) alter the ingestive behavior of the rat and (b) if altered, whether the pattern of deficit revealed would be similar to or different from that obtained by sectioning each of the individual nerves separately. Remarkably, intake-based preference was unaffected by an approximately 80% reduction in taste receptors. Lingual gustatory denervation failed to affect the preference for any of the normally-preferred stimuli. Preference for only two of the 8 normally-avoided solutions was increased following the combined nerve cuts. In contrast, examination of oral motor taste-reactivity responses revealed that combined nerve sections significantly reduced the number of ingestive responses elicited by 5 or 6 normally-preferred and 5 of 8 normally-avoided stimuli. In addition, the pattern of deficits in taste-elicited oral motor responses resulting from the combined sections was different from that predicted by summing the effects of the individual nerve sections. We had shown that CTX did not alter aversive behavior to quinine whereas CPX did reduce these responses but did not affect their concentration dependence. Neither CTX nor GPX affected oral motor responses elicited by sucrose. Combined nerve section, by contrast, completely eliminated the concentration-dependent increases in aversive responses to quinine and ingestive responses to sucrose and glycine. In fact, CTX + GPX profoundly reduced the oral motor behavior elicited by all of the chemical stimuli examined.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The tumour-inhibiting potential of the progesterone antagonist Onapristone in the human mammary carcinoma T61 in nude mice.

The progesterone antagonist Onapristone proved to possess strong tumour-inhibiting activity in a panel of experimental mammary carcinomas. Its underlying mechanism of action is due to a progesterone-receptor-mediated induction of terminal differentiation and a specific blockade of the cell cycle and is also present in the absence of progesterone as was shown in the MXT mammary tumour. To prove this further, the tumour-inhibiting activity of Onapristone was investigated in the human postmenopausal T61 mammary tumour implanted in castrated male nude mice. Whereas Onapristone given alone had no effect on growth of established tumours, after stimulation of the relatively low progesterone receptor content of this tumour line with an oestrogen, Onapristone significantly inhibited tumour growth. Thus, we suggest that Onapristone exerts its antitumour action via progesterone receptors. As there is no endogenous progesterone in these mice, the tumour-inhibiting activity of Onapristone is not primarily due to a classical antihormonal effect.

Animals↗

PubMed1992

Parabrachial gustatory lesions impair taste aversion learning in rats.

Lesions in the gustatory zone of the parabrachial nuclei (PBN) severely impair acquisition of a conditioned taste aversion (CTA) in rats. To test whether this deficit has a memorial basis, intact rats (n = 15) and rats with PBN lesions (PBNX; n = 10) received seven intraoral taste stimulus infusions (30 s, 0.5 ml) distributed over a 30.5-min period after either LiCl or NaCl injection. This task measures the rapid formation of a CTA and has minimum demands on memory. LiCl-injected intact rats progressively changed their oromotor response profile from one of ingestion to one of aversion. NaCl-injected intact rats did not change their ingestive pattern of responding. In contrast, there was no difference between LiCl- and NaCl-injected PBNX rats. These same PBNX rats failed to avoid licking the taste stimulus when tested in a different paradigm. A simple impairment in a memorial process is not likely the basis for the CTA deficit.

Afferent Pathways↗

PubMed1992

A quantitative comparison of taste reactivity behaviors to sucrose before and after lithium chloride pairings: a unidimensional account of palatability.

Alterations in the motivation to ingest sucrose can be quantified by measuring the number and type of oral motor and somatic responses (i.e., taste reactivity [TR]) that are elicited by sucrose. In 2 experiments, rats had intraorally infused sucrose paired with LiCl injections for several trials, or they were injected with LiCl and had sucrose infused every 5 min during the 30-min postinjection period (data from Spector, Breslin, & Grill, 1988). In both experiments, ingestive TR responses decreased, whereas aversive TR responses increased over trials. Individual response components that comprise the ingestive and aversive categories followed the same trends of increase or decrease but changed at different rates as a function of number of trials or exposures. Overall, the array of response components could be projected onto a single unidimensional scale of palatability to capture the motivational states that ranged from acceptance to rejection.

Animals↗

PubMed1992

Sham feeding in intact and chronic decerebrate rats.

In the traditional sham-feeding paradigm, the amount of sugar solution consumed by the rat is influenced by its concentration and the open or closed condition of the gastric fistula. The present experiments examine: 1) whether sham intake effects obtained under the "intraoral intake" paradigm, developed to explore controls of ingestion in otherwise aphagic preparations such as the decerebrate, are similar to those of previous studies in which intact rats obtained the fluid stimulus by spout licking; and 2) whether chronic decerebrate and intact rats show a similar elevation of their sucrose intake when ingesting with an open (sham intake) vs. closed gastric fistula. Experiment 1 showed that sham intraoral intake exceeded intake in the closed condition only for sucrose concentrations greater than 0.1 M. After it was established that the results obtained with the intraoral paradigm were consistent with those reported in the literature, the new paradigm was applied to the chronic decerebrate rat in experiment 2 to determine whether forebrain structures are necessary for sham-feeding effects. The effect of sucrose concentration and fistula condition on the behavior of chronic decerebrates was similar to that of intact rats. Like intact rats, decerebrate rats consumed more sucrose in the open condition but only for concentrations exceeding 0.1 M. This concentration-dependent sham sucrose intake of chronic decerebrate rats provides compelling evidence that the integration of sucrose's taste and postingestive effects that modulates ingestive behavior can be accomplished by the caudal brain stem.

Analysis of Variance↗

PubMed1992

Salt taste discrimination after bilateral section of the chorda tympani or glossopharyngeal nerves.

Gustatory deafferentation of the anterior tongue by bilateral section of the chorda tympani nerve, which removes only 15% of the total taste buds in the rat, severely impaired the rat's ability to discriminate NaCl from KCl. The discrimination deficit was selective. Denervated rats were able to discriminate sucrose from quinine. Despite eliminating four times as many taste buds by bilateral section of the glossopharyngeal nerve, posterior lingual deafferentation had no effect on NaCl vs. KCl discrimination performance. Collectively, these data suggest that afferents in the chorda tympani nerve provide the highest degree of disparity between the peripheral signals representing NaCl and KCl. Electrophysiological findings of others implicate the sodium-specific afferents that appear to exclusively exist in the chorda tympani nerve as the critical elements subserving the NaCl vs. KCl discrimination.

Animals↗

PubMed1992

Dynamics of gastric emptying during and after stomach fill.

Gastric contents were sampled at various points during and after intragastric infusions of glucose solution (6.25, 12.5, 25%) delivered at rates typical of normal ingestion in the rat. The postinfusion results were consistent with those reported in the literature in that glucose solute emptied at a relatively stable rate over time and across stimulus concentrations. During fill (1.0 ml/min; experiment 1), by contrast, solute (caloric) emptying rate increased about threefold as stimulus concentration was raised. For each concentration, emptying rate was uniformly higher during than after fill (approximately 4 times higher at the lowest concentration). In experiment 2, gastric emptying rate during 12-min intragastric infusions of 12.5% glucose varied directly with the volumetric rate (0.5, 1.0, 2.0 ml/min) at which they were delivered. These results show that different rules govern gastric emptying during and after stomach fill. The results also suggest that a large proportion of a liquid meal may empty before feeding is terminated and that variations in the rate of ingestion could affect the gastric/postgastric distribution of ingesta and, in turn, the satiation process.

Analysis of Variance↗

PubMed1991

Central gustatory lesions: I. Preference and taste reactivity tests.

Bilateral electrophysiologically guided lesions were placed in the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial thalamic nucleus (VPMpc) of rats, and 15-min intake and taste reactivity (TR) responses elicited by 3 concentrations each of sucrose, NaCl, HCl, and quinine (Q) HCl were subsequently measured. Compared with controls, NST lesions had no significant effects on intake, and rats with PBN lesions consumed significantly more QHCl, sucrose, NaCl, and HCl. Thalamic lesions decreased sucrose intake. Analysis of TR responses showed that the QHCl threshold for aversive responses increased after VPMpc, PBN, and NST lesions. Rats with NST or PBN lesions were unresponsive to increasing sucrose concentration. TR responses elicited by NaCl and HCl were similar across the groups.

Afferent Pathways↗

PubMed1991

Central gustatory lesions: II. Effects on sodium appetite, taste aversion learning, and feeding behaviors.

Intake and taste reactivity tests were used to determine the effects of bilateral lesions of the gustatory portions of the nucleus of the solitary tract (NST), the parabrachial nucleus (PBN), and the ventral posteromedial nucleus of the thalamus (VPMpc) on several complex ingestive behaviors. In the 1st experiment, lesions of the PBN and the NST blocked, and VPMpc lesions impaired, the behavioral expression of salt appetite. In the 2nd experiment, alanine was paired with injections of LiCl. Control rats as well as rats with NST and VPMpc lesions acquired the taste aversion, but rats with PBN lesions did not. In the 3rd experiment, all animals increased their food intake after injections of 2 U/kg insulin and 250 mg/kg 2-deoxy-D-glucose, and their food intake was suppressed after nutritive stomach loads.

Afferent Pathways↗

PubMed1991

Pharmacokinetics of droloxifene and its metabolites in breast cancer patients.

Pharmacokinetics and metabolism of droloxifene, a new antiestrogenic drug, have been investigated by single- and multiple-dose studies in postmenopausal patients with advanced breast cancer. Short terminal elimination half-life, low accumulation, and improved drug tolerability are the most striking features of this safe and effective new antiestrogen. Bioequivalence of film-coated tablet, tablet, and standard solution of droloxifene has been shown. The concentrations of droloxifene and its metabolites have been determined by a highly selective HPLC method.

Administration, Oral↗

PubMed1991

[Plasma lipoprotein fractions in high-dose medroxyprogesterone acetate therapy in metastatic breast cancer].

Metabolic disorders induced by synthetic gestagens have been discussed under the aspect of single endocrine parameters or the carbohydrate or lipid metabolism. In order to obtain more complex information a prospective study of 26 patients was performed, who were treated with 1,000 mg medroxyprogesterone acetate (MPA) per day over a period of 5 weeks as a second-line therapy of breast cancer. Before treatment and afterwards once a week the serum concentrations of MPA, androstenedione, DHEA-S, cortisol, prolactin, insulin, c-peptide, glucose, cholesterol, triglycerides, phospholipids and the lipoprotein fractions (VLDL, IDL, LDL, HDL) were analyzed. Besides the reduction of the androgens and changes in the glucose regulation significant effects on the lipoprotein metabolism were observed, leading to the conclusion that under high-dose gestagen therapy very complex interactions of the endocrine and metabolic system occur.

Antineoplastic Agents↗