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Biomedical subjects

I L Bernstein

Publications and source records attributed to I L Bernstein.

At least 19 recordsLinked to original sources
PubMed1997

Ethanol-induced c-Fos expression in rat lines selected for low and high alcohol consumption.

Selectively bred rat lines, developed to model genetic contributions to alcohol abuse, include the Indiana alcohol-preferring (P) and alcohol-nonpreferring (NP) lines, and the Alko-Alcohol (AA) and Alko-Nonalcohol (ANA) lines. Preferring and nonpreferring lines were compared in their response to intraperitoneal injection of either ethanol or isotonic saline using c-Fos expression as a marker of neuronal activity. Although line differences were noted in several brain regions, the principal finding was that alcohol-nonpreferring lines (NP and ANA) displayed greater c-Fos expression in the locus coeruleus (LC) relative to the alcohol-preferring lines (P and AA) following injection of 3.0 g ethanol/kg. These data point to the LC as an area which may play a role in the differences in voluntary ethanol consumption between rat lines genetically bred for low and high ethanol preference.

Alcohol Drinking↗
PubMed1997

Development of the enhanced neural response to NaCl in Fischer 344 rats.

To examine the development of strain differences in the response of the chorda tympani nerve (CT) to NaCl, integrated CT responses to NaCl were recorded from Wistar and F344 rats between 15 and 36 days old. NaCl responses before and after the application of amiloride were expressed relative to 0.5 M NH4Cl as a standard. At 15-17 days old, there were no significant strain differences in the magnitude of NaCl responses. Strain differences emerged at 21-23 days old with responses of F344 rats significantly higher than those of Wistars; these differences became more pronounced at 34-36 days old. Amiloride significantly reduced responses to NaCl at all ages and eliminated any differences between the strains. Changes in neural responsiveness correspond with the emergence of the behavioral expression of F344 salt aversion.

Amiloride↗
PubMed1997

Prevalence of human seminal plasma hypersensitivity among symptomatic women.

BACKGROUND: Experience with human seminal plasma hypersensitivity in the last decade has led to increased physician awareness of symptoms consistent with human seminal plasma sensitization in women. Incidence and prevalence of human seminal plasma hypersensitivity in women are unknown. OBJECTIVE: A questionnaire survey was distributed to determine the prevalence of human seminal plasma hypersensitivity among a population of women suspected of having this disorder. METHODS: A questionnaire designed to elicit age, symptoms, duration of symptoms, number of sexual partners, time to onset of symptoms after first human seminal plasma exposure, onset of symptoms after first intercourse, recent gynecologic procedures, history of atopy, vaginitis, food or drug allergy and family history of atopy was distributed to 1,073 women who suspected they had symptoms consistent with human seminal plasma hypersensitivity. Women were considered "possible" for human seminal plasma hypersensitivity if they reported two or more symptoms consistent with localized or systemic human seminal plasma hypersensitivity. Women were considered "probable" for disease if they fulfilled the "ultimate criterion" defined as complete prevention of symptoms with a condom. Women with "possible" localized or systemic human seminal plasma hypersensitivity who had persistent symptoms despite use of a condom served as cohort control groups. RESULTS: Two-hundred sixty-six women reported symptoms "possible" for human seminal plasma hypersensitivity (88 localized and 178 systemic). When the "ultimate criterion" was applied, 130 (46 localized and 84 systemic) of the 266 women were identified as having "probable" human seminal plasma hypersensitivity. The responses to most of the questions from each group were very similar. A significantly shorter time interval to symptom onset after initial human seminal plasma exposure was more common for women with "probable" localized human seminal plasma hypersensitivity compared with their cohort control group (49 months versus 108 months; P < .02) whereas a significantly increased number of women with "probable" systemic human seminal hypersensitivity gave positive food allergy histories compared with their cohort control group (31 versus 20; P < .05). Atopy did not appear to be a risk factor for human seminal plasma hypersensitivity. CONCLUSIONS: Evaluation of women with symptoms suggestive of human seminal plasma hypersensitivity using a validated questionnaire indicates that this disorder is more common than previously recognized.

Adult↗
PubMed1997

Dopamine and sodium appetite: antagonists suppress sham drinking of NaCl solutions in the rat.

Sodium (Na) ingestion in rats depleted of Na is a strong, motivated behavior that is enhanced further when depleted rats are sham drinking. Dopamine plays a critical role in motivation, including reward associated with consumption of palatable tastes. The present studies assessed the role of dopamine in real and sham drinking of NaCl solutions after Na depletion with the diuretic furosemide (10 mg/kg). Dopamine (D2) receptor antagonists were evaluated (Haloperidol [0.1 mg/kg] and raclopride [0.2 mg/kg]), for their effects on sham and real drinking of 0.3 M NaCl. Sham drinking was markedly reduced by both antagonists whereas real drinking was unaffected. These effects did not appear to be due to malaise or suppression of motor behavior because drug-treated animals were able to increase ingestion substantially when offered less concentrated NaCl (0.1 M). These results suggest that the positive motivating properties of NaCl stimulation in depleted, sham-drinking rats are mediated by central D2 receptors.

Animals↗
PubMed1997

Central infusion of GLP-1, but not leptin, produces conditioned taste aversions in rats.

Leptin (ob protein) and glucagon-like peptide-1-(7-36) amide (GLP-1) are peptides recently proposed to be involved in the regulation of food intake. Although the ability of exogenous leptin and GLP-1 to modulate consummatory behavior is consistent with the suggestion that these peptides are endogenous regulatory agents, central administration of these peptides may have aversive side effects, which could explain the anorexia. In the present experiment, exposure to a saccharine taste was immediately followed by central administration of leptin or GLP-1 to determine if these drugs could produce a conditioned taste aversion (CTA) in rats. At doses equated for producing comparable reductions in short-term food intake, GLP-1, but not leptin, generated a robust CTA. Although leptin caused no aversion, this peptide was the only drug to cause relatively long-term reductions in food consumption (16 h) and body weight (24 h). Hence, the results indicate that central GLP-1 produces aversive side effects, and it is argued that these nonspecific effects may explain the anorectic actions of GLP-1.

Animals↗
PubMed1996

Forebrain contribution to the induction of a brainstem correlate of conditioned taste aversion: I. The amygdala.

The induction of c-Fos-like immunoreactivity (c-FLI) in the intermediate division of the nucleus of the solitary tract (iNTS) has been shown to be a reliable cellular correlate of the acquisition and/or behavioral expression of a conditioned taste aversion (CTA). To begin to define neuroanatomical structures and pathways that contribute to this cellular response and to CTA learning in general, electrolytic lesions of the amygdala were combined with immunostaining for c-FLI. Rats were given either unilateral or bilateral electrolytic lesions of the amygdala or "sham' operations. Following surgery "paired' animals were given a single conditioning trial consisting of intraoral infusion of 5 ml 0.15% sodium-saccharin followed by injection with LiCl (0.15 M, 20 ml/kg, i.p.) while "unpaired' controls received a non-contingent saccharin-LiCl presentation. When tested, unilateral-lesioned rats displayed a CTA by rejecting the saccharin, but increases in c-FLI were evident only on the side of the iNTS contralateral to the lesion. Rats with bilateral lesions showed no evidence of having acquired a CTA and no increase in c-FLI in iNTS relative to unpaired controls. These findings support involvement of amygdala in CTA learning and suggest that a lateralized connection between amygdala and iNTS is necessary for the conditioned c-FLI which is induced by exposure to a conditioned aversive taste.

Amygdala↗
PubMed1996

Workshop overview. Identification of respiratory allergens.

A variety of chemicals and proteins can sensitize the respiratory tract. Among these are materials of industrial importance, including certain diisocyanates, acid anhydrides, reactive dyes, and enzymes. Currently, no widely accepted or well-validated methods for the prospective identification of respiratory allergens exist. Most progress has been made with guinea pig methods where sensitizing potential is measured usually by assessment of changes in pulmonary function induced following sensitization and challenge. However, these methods are often prohibitively expensive, particularly for screening purposes. A number of alternative approaches are under consideration and are described here. The nature of the health problems associated with occupational respiratory sensitization, chemical structure-activity analyses as a tool for detecting pulmonary allergens, approaches used to test for respiratory allergens in guinea pigs, and alternative approaches using mice are all discussed. Finally, regulatory issues and needs with respect to respiratory sensitization are outlined.

Allergens↗
PubMed1996

Retention of conditioned taste aversion to NaCl after chorda tympani transection in Fischer 344 and Wistar rats.

Fischer 344 (F344) rats fail to prefer sodium chloride (NaCl) solution to water, and this behavior is dramatically altered by bilateral transection of the chorda tympani nerve (CTX). Tests of retention and generalization of a conditioned taste aversion (CTA) to 0.15 M NaCl were used to assess alterations in salt taste perception after CTX. A CTA was established to 0.15 M NaCl in groups of F344 and Wistar rats after two pairings with LiCl (IP, 2% body weight; 0.15 M). After conditioning, animals received bilateral CTX or sham operations. Approximately 2 weeks after surgery animals were tested for retention of the CTA. Aversion to 0.15 M NaCl was evident in CTX and SHAM rats that had been conditioned prior to surgery, with no apparent difference in magnitude as a function of surgical condition. Thus, although CTX profoundly alters F344 rats' hedonic response to NaCl, it does not alter perceptual characteristics so markedly that NaCl is no longer recognized as the stimulus presented during aversion conditioning. Rather these studies suggest that in both the F344 and Wistar strains the chorda tympani nerve is not necessary for retention of a presurgical CTA to NaCl. These studies, therefore, do not provide evidence of changes in NaCl perceptual "quality" as a consequence of CTX either in F344 rats, where such changes were indicated by the preference data, or in the Wistar rat, where they were not.

Afferent Pathways↗
PubMed1996

Neutral mediation of food aversions and anorexia induced by tumor necrosis factor and tumors.

Tumors often cause declines in food intake and body weight, a condition referred to as tumor anorexia. A macrophage-derived peptide known as tumor necrosis factor (TNF) has been proposed as an important mediator of cancer anorexia and cachexia. Our work with an animal model of this condition indicates that strong learned aversions to the available diet arise in rats bearing implanted tumors and that these aversions contribute significantly to depressions in food intake and body weight. Lesions of the area postrema and nearby caudal medial nucleus of the solitary tract (APcmNTS) markedly attenuate both the learned aversions and the anorexia induced by tumor growth. A strikingly similar pattern of effects on tumor-induced aversions and anorexia was seen after subdiaphragmatic vagotomy and after capsaicin treatments. The similarity in the effects of all three treatments suggest that they involve interruption of the same system, presumably afferent signals conveyed by the vagus nerve to the nucleus of the solitary tract. The extent to which peripheral TNF administration generates symptoms similar to those produced by tumor growth was also examined. TNF administration was associated with the development of strong aversions to a novel but not a familiar diet. Area postrema lesions were found to significantly attenuate the effects of TNF on novel diet intake and preference. These observations provide parallels between the effects of TNF and the effects of tumor growth on diet aversions and food intake.

Animals↗
PubMed1996

A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma. Auranofin Multicenter Drug Trial.

BACKGROUND: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. OBJECTIVES: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. METHODS: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring > or = 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was "therapeutic success" or reduction of daily corticosteroid use by 50% or more. RESULTS: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) (p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline (p < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (> or = 50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) (p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group (p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. CONCLUSIONS: Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma.

Administration, Oral↗
PubMed1996

Neonatal chorda tympani transection alters adult preference for ammonium chloride in the rat.

The immature gustatory system of the neonatal rat is characterized by sensitivity to disruption by early interventions such as receptor or nerve damage. The present studies examined the effect of chorda tympani transection (neoCTX) of neonates on adult preference for salt and nonsalt stimuli. NeoCTX at 10 days of age led to a striking change in adult rats' preference for NH4Cl solutions but little change in preference for other solutions, including NaCl and KCl. Permanent anatomical effects of neoCTX included failure of the nerve to regenerate and a loss of all fungiform taste buds. Preference for NH4Cl was not due to an inability to discriminate it from NaCl. Following taste aversion conditioning to NaCl, neoCTX rats clearly distinguished between NaCl and NH4Cl. The effects on NH4Cl preference reflect a sensitive period during development because adult rats receiving similar surgery did not show any change in NH4Cl preference.

Ammonium Chloride↗
PubMed1996

c-Fos induction in rat brainstem in response to ethanol- and lithium chloride-induced conditioned taste aversions.

When consumption of a novel taste (conditioned stimulus; CS) is followed by exposure to a toxin, organisms will avoid consumption of that taste in the future. This learned response, known as a conditioned taste aversion (CTA), can be demonstrated using a variety of drugs, including lithium chloride (LiCl) and ethanol. c-Fos immunohistochemistry was used to examine neural activation in the rat brainstem associated with drug administration and with a CS taste previously paired with these drugs. Relative to saline controls, animals injected with either LiCl (76 mg/kg) or ethanol (3.5 g/kg) displayed greater c-Fos expression in area postrema, nucleus of the solitary tract (NTS), and lateral parabrachial nucleus. At these doses, LiCl- and ethanol-injected groups did not differ from each other. For establishing a CTA, intraoral infusion of a 0.15% saccharin solution was followed by injection of either LiCl or ethanol. Both LiCl and ethanol produced quantitatively similar CTAs. Relative to unpaired control groups, saccharin paired with either drug induced significant c-Fos expression in NTS. Thus, like LiCl, ethanol and tastes that have become aversive by virtue of their association with ethanol activate brainstem regions hypothesized to play a role in CTA learning.

Animals↗
PubMed1996

Sodium appetite in the sham-drinking rat after chorda tympani nerve transection.

Sodium depletion in the neurologically intact rat (Intact) produces a prompt and robust intake of NaCl. After chorda tympani nerve transection (CTX), there is a longer latency and a reduced intake of NaCl. The CTX rat depends on remaining gustatory and postingestive information to direct NaCl intake. In the present study, the effect of the removal of the postingestive signals of ingested NaCl (by means of a chronic gastric fistula) on the NaCl intakes and licking patterns of Intact and CTX rats was studied. When the gastric fistula was open (Sham), ingested NaCl did not pass beyond the stomach, thus negative postingestive stimulation was absent. After overnight sodium depletion, when postingestive stimulation was present (i.e., gastric fistula closed; Real), the CTX group drank significantly less 0.3 M NaCl than the Intact group over the 2-h test [11.7 +/- 1.6 (CTX) vs. 15.3 +/- 2.8 (Intact) ml]. In contrast, when postingestive signals were absent (i.e., Sham) the Intact group ingested 52.5 +/- 4.4 ml, whereas the CTX group had ingested only 12.4 +/- 3.1 ml of 0.3 M NaCl. Lickometer data analysis revealed that even during the first minute of the test the CTX/Real group generated significantly fewer licks than any of the other groups. Thus, although the CTX group was sensitive to inhibitory postingestive signals in the early portion of the appetite test, the absence of these signals did not release the robust and sustained intake of NaCl characteristic of the Intact group. These results suggest that information provided by the chorda tympani nerve is critically important to the strong motivational properties of NaCl after sodium depletion.

Animals↗
PubMed1996

Central infusions of leptin and GLP-1-(7-36) amide differentially stimulate c-FLI in the rat brain.

Recently, glucagon-like peptide-1-(7-36) amide (GLP-1) and leptin have been implicated in the regulation of food intake. In the present study, we compared the effects of third ventricular administration (i3vt) of leptin (3.5 micrograms) and GLP-1 (10.0 micrograms) on short-term food intake and c-Fos-like immunoreactivity (c-FLI) in hypothalamic, limbic, and hindbrain areas in the rat. Relative to controls, infusion of leptin or GLP-1 (3 h before lights off) significantly reduced food intake over the first 2 h in the dark phase (53 and 63%, respectively). In different rats, infusion of leptin or GLP-1 elevated c-FLI in the paraventricular hypothalamus and central amygdala. Furthermore, leptin selectively elevated c-FLI in the dorsomedial hypothalamus, whereas GLP-1 selectively elevated c-FLI in the nucleus of the solitary tract, area postrema, lateral parabrachial nucleus, and arcuate hypothalamic nucleus. The fact that most of the c-FLI after leptin or GLP-1 administration was observed in separate regions within the central nervous system (CNS) suggests different roles for leptin and GLP-1 in the CNS regulation of food intake and body weight.

Animals↗
PubMed1996

Taste aversion learning in fyn mutant mice.

Conditioned taste aversion (CTA) learning is a robust form of classical conditioning in which animals rapidly associate a flavor with aversive internal symptoms. The present study assessed CTA learning in transgenic mice deficient in a specific nonreceptor tyrosine kinase (the fyn mutant). Fyn mutants show impaired long-term potentiation and marked deficits in acquisition of spatial learning tasks. To assess whether they are also impaired in CTA learning, fyn mutant and wild-type mice received 2 conditioning trials consisting of access to a flavored solution followed by administration of LiCl. Fyn mutant mice acquired significant CTAs following a single conditioning trial and these aversions were comparable to those seen in wild-type mice. These results indicate that the fyn mutation does not interfere with the acquisition of CTAs and hence that this mutation is not associated with a global learning deficit.

Animals↗
PubMed1995

c-Fos induction in response to taste stimuli previously paired with amphetamine or LiCl during taste aversion learning.

Amphetamine and lithium chloride (LiCl) are both effective unconditioned stimuli (USs) in the establishment of conditioned taste aversions (CTA) in the rat. However, the mechanism of action of these drugs is quite different with the area postrema and related emetic circuitry critical to the response to LiCl but not amphetamine. c-Fos immunohistochemistry was used to define brain regions activated during drug administration and during expression of a CTA using either amphetamine or LiCl as the US drug. Administration of LiCl induced dense c-Fos-like immunoreactivity (c-FLI) in the nucleus of the solitary tract (NTS) while amphetamine induced only light staining in this area. A conditioned stimulus (CS) saccharin solution paired with amphetamine, however, was associated with c-FLI in NTS in a pattern quite similar to that seen to a LiCl-paired CS. This suggests that the pattern of c-Fos expression to a taste CS after conditioning is characteristic of aversion conditioning, in general, and appears not to represent a matching of the conditioned response to specific unconditioned effects of the drug. To examine this conditioned response further, c-FLI to the aversive saccharin CS was compared to the response to quinine hydrochloride, which is innately aversive. Although behaviorally the animals' ingestive responses were quite similar, the saccharin CS induced significant elevations of c-FLI in NTS whereas the quinine did not. Thus, a taste which had become aversive by virtue of conditioning induced c-FLI expression in NTS while a taste which was inherently aversive did not.

Amphetamine↗