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PubMed2001

Serotonin depletion attenuates cocaine seeking but enhances sucrose seeking and the effects of cocaine priming on reinstatement of cocaine seeking in rats.

RATIONALE: Acute serotonin (5-HT) depletion by the tryptophan hydroxylase inhibitor, para-chlorophenylalanine, attenuates cocaine seeking in rats. OBJECTIVE: The present study examined the effects of chronic 5-HT depletion on cocaine- and sucrose seeking using the 5-HT-selective neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). METHODS: Separate groups of rats were trained to lever press for cocaine infusions (0.33 mg/kg/0.1 ml, i.v.) or for sucrose pellets (45 mg Noyes) on a fixed ratio (FR) 1 schedule of reinforcement during daily 2-h sessions. Subsequently, animals received i.c.v. infusions of either vehicle or 5,7-DHT (150 microg/6 microl or 200 microg/20 microl). After a minimum of 10 days post-lesion, cocaine- and sucrose seeking were measured as lever presses in the absence of reinforcement (extinction). Some cocaine-trained animals were also assessed for the re-establishment of self-administration and reinstatement of extinguished cocaine seeking by i.v. cocaine priming injections and response-contingent presentations of cocaine-paired stimuli. RESULTS: 5-HT depletion by the 150 microg/6 microl dose of 5,7-DHT failed to alter cocaine- and sucrose seeking despite producing a 42-77% depletion of 5-HT in limbic terminal regions. The 200 microg/20 microl dose of 5,7-DHT attenuated cocaine seeking but enhanced sucrose seeking during extinction and produced a 55-85% depletion of 5-HT. In addition, cocaine-paired cues and cocaine priming reinstated cocaine-seeking behavior, and responding was enhanced in 5,7-DHT-treated animals relative to vehicle-treated controls at the 1 mg/kg/0.1 ml priming dose. However, re-establishment of cocaine self-administration was not altered by 5,7-DHT. CONCLUSION: The results suggest that 5-HT depletion may attenuate cocaine seeking but may enhance sucrose seeking when animals are tested during extinction. Furthermore, 5-HT depletion may enhance cocaine seeking produced by cocaine itself. Together these findings suggest that 5-HT depletion may have opposite effects on incentive motivation for cocaine during abstinence versus relapse.

5,7-Dihydroxytryptamine↗
PubMed1999

The effect of increased consumer demand on fees for aesthetic surgery: an economic analysis.

Economic theory dictates that changes in consumer demand have predictable effects on prices. Demographics represents an important component of demand for aesthetic surgery. Between the years of 1997 and 2010, the U.S. population is projected to increase by 12 percent. The population increase will be skewed such that those groups undergoing the most aesthetic surgery will see the largest increase. Accounting for the age-specific frequencies of aesthetic surgery and the population increase yields an estimate that the overall market for aesthetic surgery will increase by 19 percent. Barring unforeseen changes in general economic conditions or consumer tastes, demand should increase by an analogous amount. An economic demonstration shows the effects of increasing demand for aesthetic surgery on its fees. Between the years of 1992 and 1997, there was an increase in demand for breast augmentation as fears of associated autoimmune disorders subsided. Similarly, there was increased male acceptance of aesthetic surgery. The number of breast augmentations and procedures to treat male pattern baldness, plastic surgeons, and fees for the procedures were tracked. During the study period, the supply of surgeons and consumer demand increased for both of these procedures. Volume of breast augmentation increased by 275 percent, whereas real fees remained stable. Volume of treatment for male pattern baldness increased by 107 percent, and the fees increased by 29 percent. Ordinarily, an increase in supply leads to a decrease in prices. This did not occur during the study period. Economic analysis demonstrates that the increased supply of surgeons performing breast augmentation was offset by increased consumer demand for the procedure. For this reason, fees were not lowered. Similarly, increased demand for treatment of male pattern baldness more than offset the increased supply of surgeons performing it. The result was higher fees. Emphasis should be placed on using these economic relationships to expand the demand for aesthetic surgery.

Fees, Medical↗
PubMed1994

Mapping of globus pallidus and ventral pallidum lesions that produce hyperkinetic treading.

The purpose of this study was to identify sites where striatopallidal lesions produce two distinct sensory-triggered hyperkinetic syndromes: (1) exaggerated forelimb treading alone to oral taste infusions and (2) sensorimotor exaggerated treading plus enhanced aversive reactions to taste infusions. The behavioral characteristics of these syndromes have been described previously (Berridge, K.C. and Cromwell, H.C., Behav. Neurosci., 104 (1990) 778-795). Bilateral excitotoxin lesions were made using quinolinic acid (10 micrograms in 1 microliter) in the caudate/putamen, nucleus accumbens, globus pallidus or ventral pallidum/substantia innominata. In order to identify the precise center, borders, severity and size of lesion sites that caused these hyperkinetic treading syndromes, neuron counts (modified fractionator technique) and glial fibrillary acidic protein immunoreactivity (GFAP-IR) densitometry were used in a stereological mapping analysis. The site of lesions that produced the hyperkinetic treading syndrome without enhanced aversion was found to be restricted to the globus pallidus (GP). Damage exceeding 60% neuron loss bilaterally within a 0.8 x 1.0 x 1.0 mm subregion of the ventromedial GP produced this syndrome. The site of lesions that produced the combined syndrome of hyperkinetic treading and aversive enhancement was ventral to the globus pallidus, within the ventral pallidum/substantia innominata (VP/SI). Damage exceeding 70% neuron loss bilaterally within a 1.0 x 0.5 x 1.0 mm diameter subregion of the ventromedial ventral pallidum/substantia innominata produced this syndrome. This subterritory was located immediately lateral to the border of the lateral hypothalamus. Bilateral lesions to the caudate/putamen or nucleus accumbens did not produce either hyperkinetic treading syndrome. These results are discussed in terms of the connectivity of the ventral pallidal/substantia innominata and globus pallidus regions and in terms of neuropathological models of hyperkinetic disorders.

Animals↗
PubMed2002

Hedonic response to sucrose solutions and the fear of weight gain in patients with eating disorders.

Previous research has shown that patients with bulimia nervosa (B), anorexia nervosa, restricting type, or restrictive-anorectic (RA), and anorexia nervosa, binge eating, purging type, or anorectic-bulimic (AB) exhibit a reduced hedonic response to sucrose compared with control subjects. We hypothesized that this response could be linked to an excessive fear of weight gain rather than a decreased ability to experience pleasure. We therefore compared the hedonic responses to sucrose solutions in B, RA and AB women (n=20/group) in two different conditions: sucrose solution swallowed vs. sucrose solution spit. Under double-blind conditions and according to a Latin square design, patients received sucrose in solution (0, 5, 10, 20, and 40%) and rated each concentration for pleasantness on a nine-point scale. The two test conditions were randomly administered. The threshold concentration of sweet taste perception was also assessed, and the subjects filled out Chapman's Social and Physical Anhedonia Scale. The hedonic response to sucrose adjusted for the sweet taste perception threshold was significantly lower in the 'swallow' than in the 'spit' condition. There was a significant effect of sucrose concentrations as well as a significant condition by concentration interaction. When 'fear to swallow' sucrose solution responses were included as a covariate, the significant difference between the conditions of 'swallow' or 'spit' disappeared, but there was a significant concentration by condition by fear to swallow interaction and an almost significant covariate effect. When 'Drive for Thinness' on the Eating Disorder Inventory was included as a covariate, similar results were obtained. Social Anhedonia but not Physical Anhedonia correlated positively with 'Drive for Thinness' and 'fear of swallowing sucrose solutions', and correlated inversely with maximal hedonic response to the 'swallow' condition. 'We conclude that the hedonic responses to sucrose in patients with eating disorders are decreased when solutions are swallowed. This may reflect excessive fear of gaining weight rather than decreased ability to experience pleasure'.

Administration, Oral↗
PubMed1985

Clinical, endocrinologic, and biochemical effects of zinc deficiency.

The requirement of zinc for humans was recognized in the early 1960s. The causes of zinc deficiency include malnutrition, alcoholism, malabsorption, extensive burns, chronic debilitating disorders, and chronic renal diseases; use of certain drugs such as penicillamine and, in some cases, diuretics; and genetic disorders such as acrodermatitis enteropathica and sickle cell disease. The requirement of zinc is increased in pregnancy and during growth. The clinical manifestations of severe zinc deficiency include bullous-pustular dermatitis, alopecia, diarrhea, emotional disorder, weight loss, intercurrent infections, and hypogonadism in males; zinc deficiency can be fatal if unrecognized and untreated. A moderate deficiency of zinc is characterized by growth retardation and delayed puberty in adolescents, hypogonadism in males, rough skin, poor appetite, mental lethargy, delayed wound healing, taste abnormalities, and abnormal dark adaptation. In mild cases of zinc deficiency in human subjects, we have observed oligospermia, slight weight loss, and hyperammonemia. Zinc is a growth factor. As a result of its deficiency, growth is affected adversely in many animal species and humans, probably because zinc is needed for protein and DNA synthesis and cell division. The effects of zinc and growth hormone on growth appear to be independent of each other in experimental animals. Whether zinc is required for the metabolism of somatomedin needs further investigation. Thyroid and adrenal functions do not appear to change as a result of zinc deficiency. Glucocorticoids may have an effect on zinc metabolism, although the clinical relevance of this effect is not known at present. In contrast, testicular function is affected adversely as a result of zinc deficiency in both humans and experimental animals. The effect appears to be a direct one since the hypothalamic-pituitary axis is intact, and may relate to the reduction in testicular size as a result of the need for zinc in cell division. In addition, zinc is required for the function of several testicular enzymes, although a specific role in steroidogenesis has not been identified. Zinc appears to have a role in the modulation of prolactin secretion, in the secretion and action of insulin, and in the production and biologic effects of thymic hormones. It is clear that the endocrine consequences of zinc deficiency are multiple, and that continued investigation should provide additional pathophysiologic and therapeutic insights.

Burns↗
PubMedDate not supplied

Alcohol exposure during development alters social recognition and social communication in rats.

The present study examined the effects of postnatal alcohol exposure via gastric intubation on social communication of diet preference and social recognition. Rats were placed in one of three treatment groups. All treatments occurred from postnatal day (PD) 2 through 10 and Experiments 1 and 2 were conducted when the rats reached 60 and 100 days of age, respectively. Alcohol-exposed pups received a 3.0 g/kg dose of ethanol in milk solution that was delivered by insertion of PE-10 tubing down the esophagus daily from PD 2 through 10. Intubated control animals underwent intubation without ethanol or milk. Nontreated control pups were weighted daily. In Experiment 1, a nonexperimental rat was initially given access to lab chow mixed with a spice and then housed with an experimental rat for 30 min. The experimental rat was subsequently given access to two diets--one that the nonexperimental rat had consumed and a novel diet. It was found that the alcohol-exposed females consumed a greater percent of the communicated diet than the control females. In Experiment 2, the experimental rats were first exposed to a juvenile for 5 min and then exposed to the same juvenile after a delay of 30 or 90 min. Investigation time was recorded in both sessions and a reduction of investigation time in the second session is an indicator of social recognition memory. Alcohol-exposed rats of both sexes had poorer memory of a juvenile than both control groups after a 90-min delay. Together, these data indicate that basic components of social behavior may be altered by alcohol exposure during development.

Alcohol-Related Disorders↗
PubMed1998

Zopiclone in the treatment of insomnia: an open clinical trial.

The purpose of this study was to examine the efficacy and adverse effects of zopiclone in Thai psychiatric patients. Thirty-two insomniac outpatients with a variety of diagnoses participated in this study. Zopiclone at the dose of 7.5-15 mg was administered 15 minutes before bedtime. The sleep-questionnaire items included: 1) sleep induction; 2) duration of sleep; 3) number of awakenings, 4) sleep quality; 5) dream incidence; and 6) condition in the morning. The mean scores of each item were compared by using pair t-test. One week after treatment, significant improvement was found in all items, except item 5. In comparison between sleep at 1 week and 3 weeks after treatment, further improvement was still found in the first three items. The adverse effects found were bitter taste, drowsiness, and headache. In conclusion, zopiclone is an effective hypnotic with few adverse effects.

Adult↗
PubMed1999

Prophylactic Lactobacillus GG reduces antibiotic-associated diarrhea in children with respiratory infections: a randomized study.

OBJECTIVES: Antimicrobial treatment may disturb the colonization resistance of gastrointestinal microflora, which may induce clinical symptoms, most commonly diarrhea. The severity of antibiotic-associated diarrhea may range from a brief, self-limiting disease to devastating diarrhea with electrolyte disturbances, dehydration, crampy abdominal pain, pseudomembranous colitis, toxic megacolon, or even death. The incidence of diarrhea in children receiving a single antimicrobial treatment is unclear. In addition to more critical use of antimicrobials, adjunctive preventive measures to antibiotic-associated diarrhea are needed. The objective of this study was to evaluate the incidence of diarrhea after antimicrobial treatment in children with no history of antimicrobial use during the previous 3 months. Another aim of this study was to assess the preventive potential of Lactobacillus rhamnosus GG (Lactobacillus GG; American Type Culture Collection 53103), a probiotic strain with a documented safety record and a therapeutic effect in viral gastroenteritis on antibiotic-associated diarrhea. METHODS: Oral antimicrobial agents were prescribed for the treatment of acute respiratory infections at the clinics of the Health Care Center of the City of Tampere or Tampere University Hospital, Finland, to 167 patients who were invited to participate in the study. Of the patients, 48 were lost to follow-up; therefore, the final study population consisted of 119 children from 2 weeks to 12. 8 years of age (mean: 4.5 years). All study subjects met the inclusion criteria: they had not received any antimicrobial medication during the previous 3 months, they did not suffer from gastrointestinal disorders, and they did not need intravenous antimicrobial treatment. The patients were randomized to receive placebo or 2 x 10(10) colony-forming units of Lactobacillus GG in capsules given twice daily during the antimicrobial treatment. Lactobacillus GG and placebo capsules were indistinguishable in appearance and taste. The parents kept a daily symptom diary and recorded stool frequency and consistency at home for 3 months. Diarrhea was defined as at least three watery or loose stools per day for a minimum of 2 consecutive days. In the case of diarrhea, viral (adenovirus, rotavirus, calicivirus and astrovirus) and bacterial (Salmonella, Shigella, Yersinia, Campylobacter, Clostridium difficile, Staphylococcus aureus, and yeasts) analyses were studied in fecal samples. The metabolic activity of the gut microflora was assessed by analysis of fecal urease, beta-glucosidase, and beta-glucuronidase activities. The primary outcome measure was diarrhea during the first 2 weeks after the beginning of the antimicrobial treatment, because this period most likely reflects the effects of antimicrobial use. Secondary outcome measures were the activities of fecal urease, beta-glucuronidase, and beta-glucosidase. RESULTS: On the entire follow-up, 80% of any gastrointestinal symptoms were reported during the first 2 weeks after the beginning of the antimicrobial treatment. The incidence of diarrhea was 5% in the Lactobacillus GG group and 16% in the placebo group within 2 weeks of antimicrobial therapy (chi(2) = 3.82). The treatment effect (95% confidence interval) of Lactobacillus GG was -11% (-21%-0%). In diarrheal episodes, the viral and bacterial analyses were positive for Clostridium difficile in 2 cases and for Norwalk-like calicivirus in 3 cases. The age of the patients with diarrhea was between 3 months and 5 years in 75% of cases in both groups. The severity of diarrhea was comparable in the study groups, as evidenced by similar stool frequency (mean: 5 per day; range: 3-6) and the duration of diarrhea (mean: 4 days; range: 2-8). The activities of fecal urease and beta-glucuronidase, but not beta-glucosidase, changed significantly after the beginning of the antimicrobial treatment in the Lactobacillus GG group and in the placebo group alike. (ABSTRACT TRUNCATED)

Anti-Bacterial Agents↗
PubMed1993

Cephalic phase insulin release in bulimia.

Cephalic phase secretions are associated with the sight, smell, and taste of food, as opposed to its postingestional consequences. These secretions are thought to influence metabolism and eating behavior. Cephalic phase insulin release (CPIR), in particular, might be related to hunger and overeating. It was hypothesized that bulimics, who often show endocrine abnormalities, may have an altered CPIR that, in turn, might be related to the precipitation and maintenance of binges. This study investigated whether (1) the profile or magnitude of the CPIR in bulimics differs from that of non-eating disordered controls, (2) food ingestion alters subsequent CPIR, and (3) mood and desire to binge are related to CPIR. Findings indicated little abnormality in bulimics' profile of insulin secretion. Although biological variables were not related to hunger or desire to binge, for bulimics, dysphoric moods were. The results may suggest more complex determinants of binge eating than physiological state alone.

Adult↗
PubMed1979

Thiamin deprivation in ventromedial hypothalamic hyperphagic rats: anorexia, specificity of food aversion, and a dietary consideration.

The anorexic consequence of thiamin deprivation was investigated in ventromedial hypothalamic (VMH) hyperphagic rats under either high-fat or low-fat thiamin-free diet conditions. The low-fat diet maintained feeding significantly longer in thiamin-deprived VMH rats than in intact rats, whereas the hig-fat diet sustained feeding in thiamin-deficient intact rats and accelerated anorexia onset in vitamin B1 deprived VMH rats. This effect was noted under both ad lib and pair-feeding conditions. Thiamin-deprived VMH rats subjected to weight control developed anorexia sooner than intact subjects regardless of the diet employed. The VMH rats fed a high-fat diet failed to resume feeding after thiamin readministration, which was interpreted as a permanent aversion to this diet. The relation between dietary intake and conditioned taste aversion is discussed with reference to the VMH and intact rat.

Animals↗
PubMed2006

Evidence for a female-specific effect of a chromosome 4 locus on anxiety-related behaviors and ethanol drinking in rats.

Previous studies using the inbred rat strains Lewis (LEW) and spontaneously hypertensive rats (SHR) led to the mapping of two quantitative trait loci, named Ofil1 (on chromosome 4 of the rat) and Ofil2 (on chromosome 7), for open-field inner locomotion, a behavioral index of anxiety. Studies using other strains showed that the region next to Ofil1 influences measures of not only anxiety but also ethanol consumption. In view of the high prevalence of psychiatric disorders such as anxiety and alcoholism, as well as the comorbidity between them, the present study was designed to better characterize the contribution of these two loci to complex emotional and consummatory responses. Rats deriving from an F2 intercross between the LEW and the SHR strains were selected according to their genotype at markers flanking the loci Ofil1 and Ofil2 and bred to obtain lines of rats homozygous LEW/LEW or SHR/SHR for each of the two loci, thus generating four genotypic combinations. These selected animals as well as purebred LEW and SHR rats of both sexes were submitted to a battery of tests including measures of locomotor activity, anxiety, sweet and bitter taste reinforcement and ethanol intake. Lewis rats displayed more anxiety-like behavior and less ethanol intake than SHR rats. Ofil1 (on chromosome 4) affected both the activity in the center of the open field and ethanol drinking in females only. These results suggest that Ofil1 contains either linked genes with independent influences on anxiety-related responses and ethanol drinking or a pleiotropic gene with simultaneous effects on both traits.

Alcohol Drinking↗
PubMed1977

Comparison of ovarian and hypothalamic obesity syndromes in the female rat: effects of diet palatability on food intake and body weight.

Both ovariectomy and hypothalamic knife cuts produced hyperphagia and obesity in adult female rats. The ovarian obesity, however, unlike hypothalamic obesity, was virtually independent of diet palatability. Ovariectomized rats became obese on quinine-adulterated diets, which completely blocked hypothalamic obesity, and they displayed little further weight gain when given a high-fat diet, which greatly potentiated hypothalamic obesity. Ovarian and hypothalamic obesity were also found to be additive irrespective of diet condition when both surgical treatments were combined in the same animal; that is, ovariectomy increased the food intake and body weight of knife-cut animals given the quinine or high-fat diet. In contrast to their dissimilar feeding effects, ovariectomy, hypothalamic cuts, and the combined surgeries, did not differentially alter the aversion to a .01% quinine solution. The results indicate that ovarian obesity and hypothalamic obesity represent two different feeding disorders and are mediated by separate neural mechanisms. The functional nature of these disorders is discussed in light of recent body weight set point interpretations.

Animals↗
PubMed1997

Genetic lesions associated with blastic transformation of polycythemia vera and essential thrombocythemia.

Polycythemia vera (PV) and essential thrombocythemia (ET) are chronic myeloproliferative disorders that may progress to acute leukemia in a subset of patients. This study aimed at investigating the genetic lesions associated with the blastic transformation of PV and ET. A panel of PV and ET cases at different stages of disease was analyzed for the presence of genetic alterations of TP53, NRAS, KRAS, and MDM2 by a combination of mutational analysis and Southern blot hybridization. The occurrence of microsatellite instability (MSI) was also tasted in selected cases. Samples of PV and ET analyzed in chronic phase disease were consistently devoid of all genetic lesions tested, suggesting that alterations of TP53, NRAS, KRAS, and MDM2 do not contribute significantly to development of chronic phase PV and ET. Conversely, mutations of TP53 were detected in 7/15 (46.6%) blastic phase cases, including 3/5 PV and 4/10 ET. In blastic phase patients for whom the corresponding chronic phase DNA was also available, it could be documented that the genetic lesion had arisen at the time of blastic transformation. In addition to TP53 mutations, cases of blastic phase PV and ET occasionally harbored mutations of NRAS (one case of blastic phase ET) or displayed MSI (one case of blastic phase PV). These data indicate that inactivation of TP53 is a relatively frequent event associated with the blastic transformation of PV and ET and may be responsible for the tumor progression of these disorders.

Adult↗