Gustatory differences in hypothyroid and hyperthyroid tasters and non-tasters

Gustatory differences in Phenylthiocarbamide (PTC) tasters and non-tasters were studied in hypothyroid and hyperthyroid subjects. After presenting for PTC sensitivity, gustatory responses to 7 dilutions of test solutions for glucose (sweet), sodium chloride (salt), citric acid (sour) and quinine sulphate (bitter) were studied in PTC tasters and non-tasters. The intensity and pleasantness responses for 4 basic tastes were measured on a 7-point and 6-point category scale respectively. Sixty percent of subjects of hyperthyroid and 40% of hypothyroid subjects were tasters. Hypothyroid subjects showed more gustatory differences as compared to hyperthyroids. The diminished intensity perception for sweet and bitter taste was much more prominent in non-tasters than tasters hypothyroids. The greater hedonic value for salt was largely observed among hypothyroid tasters.     

Dietary salt intake and the clonidine suppression test

We studied the effects of one week of dietary salt restriction and one week of salt loading on hemodynamic and plasma catecholamine responses to clonidine. Among 11 outpatients with essential hypertension, urinary sodium excretion averaged 29 mEq/d during salt restriction and 322 mEq/d during salt loading. Among eight inpatient normotensive subjects, urinary sodium excretion averaged 11 mEq/d during salt restriction and 300 mEq/d during salt loading. Three hours after administration of oral clonidine 300 micrograms, the hypertensive patients had an average (+/- one standard deviation) decrease in mean arterial pressure of 20 +/- 6% while receiving the low salt diet and 19 +/- 9% while taking the high salt diet, with decreases in venous plasma norepinephrine (NE) of 61 +/- 15% and 61 +/- 16%, respectively. The normotensive subjects had a decrease in mean arterial pressure of 16 +/- 8% with the low salt diet and 15 +/- 9% with the high salt diet, with decreases in venous plasma NE of 64 +/- 10% and 66 +/- 8%. Thus, in neither group were the percent decreases in plasma NE or in mean arterial pressure after clonidine affected by diet. Short-term, large-magnitude changes in dietary intake of sodium do not affect the sympathetic contribution to blood pressure as indicated by percent responses of plasma NE or of mean arterial pressure to clonidine administration.     

Behavioral processes mediating phencyclidine-induced decreases in voluntary sucrose consumption

Prior exposure to phencyclidine (PCP) has been shown to decrease voluntary sucrose consumption in rats, which may indicate reduced reward function. To further characterize the effects of PCP on sucrose consumption, we examined the dose-response relationship between PCP and sucrose consumption, the longevity of the effect, the effects of repeated injections of PCP, variation of the PCP effect across sucrose concentrations, and the effects of PCP on gustatory hedonic responses. A single injection of PCP (2.5-20 mg/kg) dose-dependently suppressed sucrose consumption 20 h post-injection, with significant decreases after 15 and 20 mg/kg PCP. These decreases were sustained three days following withdrawal from PCP. Repeated injections of PCP (7.5 mg/kg bid for 7 days) decreased sucrose consumption 20 h after withdrawal, which returned to baseline on the second day. A single injection of PCP (15 mg/kg) suppressed 0.15 M sucrose more than 1 M sucrose consumption, with no effect on 0.3 M sucrose, suggesting that PCP suppressed intake of moderately rewarding taste stimuli. Finally, a single injection of PCP (15 mg/kg) suppressed brief access (20 s) licking for the majority of concentrations of sucrose solutions offered (0.031 M, 0.062 M, 0.125 M, 0.25 M, 0.5 M, and 1.0 M), while it had no effect on licking for 0.016 M sucrose, water, or for bitter quinine hydrochloride solutions (range: 0.94 mM-30 mM), suggesting that the PCP effect is specific to palatable taste stimuli without disruption of sensitivity to taste quality or intensity. We conclude that PCP produces moderate anhedonia as reflected through a specific decrease in the sustained consumption of moderately palatable sucrose solutions.     

Quantification of suppression of bitterness using an electronic tongue.

Phospholipids, such as phosphatidic acid, suppress bitter taste without affecting other taste qualities. In the present study, we detected and quantified this suppression effect with an electronic tongue whose transducer is composed of several kinds of lipid/polymer membranes with different characteristics. We measured a phospholipid cocktail and various kinds of taste substances with five basic taste qualities. The responses to quinine hydrochloride and L-tryptophan, which have a bitter taste, were reduced as the phospholipid concentration was increased, and the responses to the other taste substances were not affected by the phospholipids, as with the human sensation test. Furthermore, the change of bitter intensity caused by phospholipid was quantified by principal component analysis and the tau scale, which expresses the relationship between taste intensity and taste substance concentration. The results are compared with those of the human sensory test and discussed.     

Taste function in methadone-maintained opioid-dependent men

It has been shown repeatedly that opioid dependence is associated with increased consumption of refined sugars. It is possible that this association results from altered taste reactivity in opioid-dependent subjects. Thus, in the present study, we compared taste responses to sweet, bitter, sour and salty solutions in methadone-maintained opioid-dependent men and healthy control subjects. The two groups did not differ in terms of rated intensity or pleasantness of sucrose (1-30%), quinine (0.001-0.005%), citric acid (0.02-0.1%) and sodium chloride (0.18-0.9%) solutions. Proportions of 'sweet-likers', i.e. subjects rating a 30% sucrose (0.88 M) solution as the most pleasant, were also similar in both groups. In line with the previous findings, the methadone-maintained subjects reported adding more table sugar to caffeinated beverages. The results of the present study suggest that changes in taste reactivity may not be responsible for altered dietary choices in opioid addicts.     

Specific sensory detection, discrimination, and hedonic estimation of nicotine enantiomers in smokers and nonsmokers: are there limitations in replacing the sensory components of nicotine?

The aim of this study was to investigate in smokers and nonsmokers (1) the olfactory and trigeminal detection of R(+)- and S(-)-nicotine and (2) the discrimination ability and hedonic estimation of nicotine enantiomers in olfactory and trigeminal concentrations. Thirty healthy male subjects (15 smokers, 15 nonsmokers) participated in the experiments. A randomized sequence of R(+)- and S(-)-nicotine stimuli (seven R(+)- and seven S(-)-nicotine stimuli) were introduced into the right nostril of the subjects using a Kobal-olfactometer. The subjects were instructed to group the stimuli into two categories (A and B). To test the role of the olfactory and the trigeminal system in this discrimination task, the authors studied the olfactory detection threshold for the "odorous" sensation and the trigeminal detection thresholds for the "burning" and "stinging" sensations. Nicotine enantiomers were presented at the individual "olfactory" and "trigeminal" concentration levels. The subjects estimated the hedonic properties using a bipolar visual analog scale (from "very unpleasant" to "very pleasant"). A statistical evaluation (t-test) revealed that the subjects were able to identify R(+)- and S(-)-nicotine at olfactory and trigeminal concentrations (p < or = 0.01, p < or = 0.001, respectively). At concentrations near the detection thresholds, i.e., clearly below subjective pain thresholds, smokers rated both nicotine stereoisomers to be significantly more pleasant than did nonsmokers (t-test, R(+)-nicotine: p < or = 0.05; S(-)-nicotine: p < or = 0.01). Increasing the concentrations to above trigeminal thresholds resulted in a difference in hedonic estimates. Smokers perceived the S(-)-isomer as being less unpleasant than nonsmokers at trigeminal concentrations (t-test, p < or = 0.001). This difference in perception might be explained by the smokers' experience with S(-)-nicotine, which is the natural nicotine enantiomer in tobacco.     

Endocannabinoid hedonic hotspot for sensory pleasure: anandamide in nucleus accumbens shell enhances 'liking' of a sweet reward.

Cannabinoid drugs such as Delta9-THC are euphoric and rewarding, and also stimulate food intake in humans and animals. Little is known about how naturally occurring endogenous brain cannabinoids mediate pleasure from food or other natural sensory rewards. The taste reactivity paradigm measures effects of brain manipulations on affective orofacial reactions to intraorally administered pleasant and unpleasant tastes. Here we tested if anandamide microinjection into medial nucleus accumbens shell enhances these affective reactions to sweet and bitter tastes in rats. Anandamide doubled the number of positive 'liking' reactions elicited by intraoral sucrose, without altering negative 'disliking' reactions to bitter quinine. Anandamide microinjections produced Fos plumes of approximately 0.02-1 mm3 volume. Plume-based maps, integrated with behavioral data, identified the medial shell of accumbens as the anatomical hotspot responsible for hedonic amplification. Anandamide produced especially intense hedonic enhancement in a roughly 1.6 mm3 'hedonic hotspot' in dorsal medial shell, where anandamide also stimulated eating behavior. These results demonstrate that endocannabinoid signals within medial accumbens shell specifically amplify the positive hedonic impact of a natural reward (though identification of the receptor specificity of this effect will require future studies). Identification of an endocannabinoid hotspot for sensory pleasure gives insight into brain mechanisms of natural reward, and may be relevant to understanding the neural effects of cannabinoid drugs of abuse and therapeutic agents.     

Taste sensitivity in pregnancy.

Taste sensitivity to Phenyl-thio-Carbamide (PTC) and glucose were studied in 150 females during the 3 trimesters of their pregnancy periods. The taste sensitivity to PTC was determined by Harris and Kalmus method. For taste intensity and hedonic evaluation, 7 concentrations of glucose solutions were used. Taste sensitivity to both PTC and glucose increases during the 1st trimester of pregnancy. In comparison to non-pregnant females (from previous study) taste thresholds and hedonics decreases in pregnancy.     

Acute effects of D-fenfluramine on simultaneous measures of aggressive escape and impulsive responses of adult males with and without a history of conduct disorder

RATIONALE: The role of serotonin in human aggression was evaluated by administering D-fenfluramine and comparing the effects on laboratory measures of aggression, escape and impulsivity among subjects with and without a history of conduct disorder. METHODS: Ten male subjects with a history of criminal behavior participated in experimental sessions that measured aggressive and impulsive responses. Five subjects had a history of childhood conduct disorder (CD+) and five control subjects did not. Aggression was measured using the Point Subtraction Aggression Paradigm (PSAP), which provides subjects with an aggressive, escape and monetary reinforced response options. Impulsive responses were measured using a paradigm that gives subjects choices between small rewards after short delays versus larger rewards after long delays. RESULTS: Acute doses (0.1, 0.2 and 0.4 mg/kg) of D-fenfluramine produced significant decreases in aggressive responses in CD+ subjects and large decreases in escape responses for CD+ subjects and smaller decreases for control subjects. Impulsive responses were decreased slightly and monetary reinforced responses were not changed in either group. Decreases in aggressive responses were not selective, since escape responses were also decreased, but such effects could not be attributed to a non-specific sedative action because monetary reinforced responses were increased and reaction times were decreased, indicative of central nervous system stimulation. CONCLUSIONS: Release of serotonin by D-fenfluramine is the possible mechanism for reductions in aggressive responses. These results are consistent with a large body of data linking reduced serotonin function and aggressive behavior.     

Decreased consumption of sweet fluids in mu opioid receptor knockout mice: a microstructural analysis of licking behavior

Rationale

Evidence suggests that the palatability of food (i.e., the hedonic impact produced by its sensory features) can promote feeding and may underlie compulsive eating, leading to obesity. Pharmacological studies implicate opioid transmission in the hedonic control of feeding, though these studies often rely on agents lacking specificity for particular opioid receptors.

Objectives

Here, we investigated the role of mu opioid receptors (MORs) specifically in determining hedonic responses to palatable sweet stimuli.

Methods

In Experiment 1, licking microstructure when consuming sucrose solution (2 to 20 %) was compared in MOR knockout and wildtype mice as a function of sucrose concentration and level of food deprivation. In Experiment 2, a similar examination was conducted using the palatable but calorie-free stimulus sucralose (0.001 to 1 %), allowing study of licking behavior independent of homeostatic variables.

Results

In Experiment 1, MOR knockout mice exhibited several alterations in sucrose licking. Although wildtype mice exhibited a twofold increase in the burst length when food deprived, relative to the nondeprived test, this aspect of sucrose licking was generally insensitive to manipulations of food deprivation for MOR knockout mice. Furthermore, during concentration testing, their rate of sucrose licking was less than half that of wildtype mice. During sucralose testing (Experiment 2), MOR knockout mice licked at approximately half the wildtype rate, providing more direct evidence that MOR knockout mice were impaired in processing stimulus palatability.

Conclusions

These results suggest that transmission through MORs mediates hedonic responses to palatable stimuli, and therefore likely contributes to normal and pathological eating.     

Selective Inhibition of Bitter Taste of Various Drugs by Lipoprotein

Previously, we demonstrated that lipoprotein composed of phosphatidic acid (PA) and -lactoglobulin (LG) selectively and reversibly suppress the frog taste nerve response to bitter substances. In the present study, we examined the effects of various lipoproteins on the taste sensation to various stimuli in humans by a psychophysical method. Among various lipoproteins composed of different of lipids and proteins, the lipoproteins composed of PA and proteins were most effective in suppressing bitter taste. The lipoproteins composed of PA and LG, bovine serum albumin, ovalbumin, -lactoalbumin or casein similarly suppressed effects on sensation of bitter taste. Using PA-LG, the effects on taste sensation to various stimuli were examined. The bitter taste of all twelve substances examined was inhibited, while saltiness of NaCl and sweetness of sucrose were not inhibited. The inhibition of bitter taste was completely reversible. Masking of the target sites for bitter substances on the taste receptor membranes with PA-LG seems to contribute to the inhibition of bitter taste. Direct binding of the bitter substances to PA-LG in the medium also contributes to the inhibition of bitter taste of certain substances. Among various drugs, basic and hydrophobic substances such as quinine, denatortium and propranolol have low taste thresholds and are said to be the most bitter. PA-LG most effectively suppressed the bitter taste of such substances. PA originates from soybeans and the proteins used except for bovine serum albumin originate from milk or eggs, and hence the lipoproteins can be safely used to mask the bitter taste of drugs.     

Ventricular fibrillation is reduced in hypothyroid rats with enhanced myocardial alpha-adrenoceptor responsiveness.

1. The severity of ventricular arrhythmias induced by coronary artery occlusion and reperfusion has been examined in control rats and animals made hypothyroid by pretreatment with 6-propylthiouracil (PTU). The maximal driving frequency and sensitivity of isolated left atria and papillary muscles to isoprenaline and to phenylephrine in the presence of propranolol, were also examined in tissues from control and hypothyroid animals. 2. Pretreatment with PTU resulted in a potentiation of responses to the alpha-adrenoceptor agonist phenylephrine in both left atria and papillary muscles, while responses to isoprenaline were depressed in left atria but unaltered in papillary muscles from hypothyroid animals. 3. In rats subject to coronary artery occlusion, PTU pretreatment reduced the incidence of ventricular fibrillation during acute myocardial ischaemia and abolished reperfusion-induced ventricular fibrillation. Mortality during myocardial ischaemia and reperfusion was also abolished. Diastolic blood pressure was similar in hypothyroid and control animals, but there was a small reduction in systolic blood pressure and a marked decrease in heart rate in PTU pretreated animals. 4. These results demonstrate that PTU-induced hypothyroidism represents a condition where cardiac alpha-adrenoceptor-mediated responses are enhanced but the severity of ischaemia- and reperfusion-induced arrhythmias is reduced.     

The hypothyroid rat as a model of increased sensitivity to dopamine receptor agonists

Control and hypothyroid rats were challenged with a range of doses (0.5-4 mumol/kg) of either the nonselective dopamine agonist, apomorphine, or the selective D2 receptor agonist. LY 171555, and their stereotyped head-down sniffing (SHDS) responses measured. The dose-response curves for both agonists were shifted to the left in the hypothyroid rats compared to water-treated controls. Increasing doses of the selective D2 antagonist, raclopride, caused a parallel shift to the right in the LY 171555-induced SHDS dose-response curve. Schild analysis revealed a decreased sensitivity to raclopride in the hypothyroid animals. The selective D1 antagonist SCH 23390 was observed to decrease the maximal response elicited by LY 171555 in a dose-dependent manner and the hypothyroid rats were more sensitive to this effect. It was concluded that hypothyroid rats showed an apparent increased sensitivity to D2 receptor agonists and a decreased sensitivity to D2 antagonists. In addition, the facilitation effect of the D1 receptor on the D2 receptor appeared less tightly coupled in the hypothyroid rats.     

Influenza vaccine and adjuvant

Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine.     

Immediate hedonic response to smoking lapses: relationship to smoking relapse, and effects of nicotine replacement therapy

OBJECTIVE AND RATIONALE: Smoking lapses represent an important juncture between smoking cessation and relapse. Nicotine replacement therapy (NRT) has been shown to decrease the risk of progression from lapse to relapse. We hypothesized that this effect might be mediated via decreases in reinforcement from smoking lapses. METHOD: We assessed 169 subjects who lapsed during treatment in a double-blind placebo-controlled study of high-dose (35 mg) nicotine patch. Following their first lapse, using an electronic diary, subjects recorded the amount they smoked, and rated the pleasantness and satisfaction ("hedonic rating") and the aversiveness of smoking. Subjects were then followed and assessed for further lapses and relapses. RESULTS: Subjects who smoked more during the first lapse had greater risk of progression [second lapse: hazard ratio (HR)=1.16, confidence interval (CI)=1.01-1.32; relapse: HR=1.22, CI=0.97-1.54]. Subjects with higher hedonic ratings of the first lapse also had a greater risk of progression to the second lapse (HR=1.08, CI=1.02-1.14) and to relapse (HR=1.26, CI=1.11-1.41). Aversive ratings had no bearing on progression. As expected, active treatment reduced the risk of both a second lapse (HR=0.54, CI=0.39-0.78) and a relapse (HR=0.22, CI=0.11-0.45). Importantly, however, NRT had no effect on hedonic ratings, amount smoked during the first lapse, or aversive ratings. CONCLUSIONS: Hedonic response to an initial lapse predicted progression to relapse, but this did not mediate the effect of NRT on progression.     

Influence of caffeine on the liking of novel-flavored soda in adolescents

Background

Soda manufacturers claim that caffeine is added to soda as a flavor enhancer, but many researchers have speculated that caffeine is added to increase the hedonic and reinforcing properties of the soda. Studies in adults have demonstrated that caffeine can condition flavor preferences when added to novel-flavored beverages.

Objectives

The purpose of this study was to test the hypothesis that caffeine added to novel-flavored drinks would increase liking and preference in adolescents.

Methods

Adolescents (n?=?99) between the ages of 12 and 17 rated and ranked seven novel soda drinks. They were then randomly assigned to consume one of these beverages paired with either caffeine (1 or 2 mg/kg) or placebo over four consecutive days and rate liking. On the final visit, participants retasted the seven beverages and provided hedonic ratings and rankings.

Results

Participants in the 2-mg/kg caffeine group increased the liking of the beverage over the exposure period after an initial decrease, but there was no change in liking for those in the placebo group or in the 1-mg/kg group. The increase in liking in the 2-mg/kg group was accompanied by a decrease in perceived bitterness, but no change in beverage ranking or consumption during the post-test.

Conclusions

Caffeine added to novel beverages results in a decrease in liking followed by an increase in liking with repeated exposures that may result from habituation to the bitterness of caffeine. Change in bitter perception may be the mechanism by which adolescents establish regular caffeine use.     

Caffeine ingested under natural conditions does not alter taste intensity

It has been reported that prolonged application of 10 micromolar (microM) caffeine (CAF) to the dorsal surface of the tongue may markedly enhance the perceived intensity of many taste stimuli, including NaCl and several noncarbohydrate sweeteners. The present study investigated the effect of oral CAF vs. placebo ingestion on perceived taste intensity. Ingestion of CAF (5.5 mg/kg) raised median salivary CAF levels to 19.8 microM at 50 minutes post-dose, when subjects evaluated the intensity of solutions of 5 noncarbohydrate sweeteners, 2 carbohydrate sweeteners, 2 bitter tastants, NaCl, citric acid, 2 odors, and a tone. Taste solutions were prepared using either 1) deionized water or 2) 10 microM CAF as the medium, and all stimuli were rated for intensity on a 9-point category scale. There was no effect of condition (CAF or placebo) or tastant medium on any response measure. The results suggest that perceptions of taste intensity are not appreciably altered under natural conditions of CAF ingestion and subsequent lingual adaptation to microM levels of CAF in saliva.     

Attenuation of saccharin-seeking in rats by orexin/hypocretin receptor 1 antagonist

Rationale

The orexin (Orx)/hypocretin system has been implicated in reward-seeking, especially for highly salient food and drug rewards. We recently demonstrated that signaling at the OxR1 receptor is involved in sucrose reinforcement and reinstatement of sucrose-seeking elicited by sucrose-paired cues in food-restricted rats. Because sucrose reinforcement has both a hedonic and caloric component, it remains unknown what aspect of this reward drives its reinforcing value.

Objectives

The present study examined the involvement of the Orx system in operant responding for saccharin, a noncaloric, hedonic (sweet) reward, and in cue-induced reinstatement of extinguished saccharin-seeking in ad libitum-fed vs food-restricted male subjects.

Methods

Male Sprague Dawley rats were fed ad libitum or food-restricted and trained to self-administer saccharin. We determined the effects of pretreatment with the OxR1 receptor antagonist SB-334867 (SB; 10–30 mg/kg) on fixed ratio (FR) saccharin self-administration and on cue-induced reinstatement of extinguished saccharin-seeking.

Results

SB decreased responding and number of reinforcers earned during FR responding for saccharin and decreased cue-induced reinstatement of extinguished saccharin-seeking. All of these effects were obtained similarly in food-restricted and ad libitum-fed rats.

Conclusions

These results indicate that signaling at the OxR1 receptor is involved in saccharin reinforcement and reinstatement of saccharin-seeking elicited by saccharin-paired cues regardless of food restriction. These findings lead us to conclude that the Orx system contributes to the motivational effects of hedonic food rewards, independently of caloric value and homeostatic needs.     

DISEASE-INDUCED CHANGES IN α-ADRENOCEPTOR-MEDIATED CARDIAC AND VASCULAR RESPONSES IN RATS

1. The physiological relevance of cardiac and vascular α-adrenoceptors may increase in disease states in which β-adrenoceptors are altered. To test this, positive inotropic and vasoconstrictor responses to phenylephrine were measured in isolated tissues from rats with experimentally-induced hyperthyroidism, hypothyroidism and diabetes as well as in genetically spontaneous hypertensive rats (SHR). 2. In left atria, positive inotropic responses to phenylephrine were increased in hypothyroid and diabetic rats and abolished in hyperthyroid and SHR. 3. In contrast, phenylephrine produced increased positive inotropy in left ventricular papillary muscles from hyperthyroid rats, increased potency in diabetic rats and negative inotropic responses in hypothyroid rats. 4. The potency of phenylephrine as a vasoconstrictor in thoracic aortic rings was increased in hyperthyroid and SHR and decreased in hypothyroid rats. 5. Thus, disease states which alter β-adrenoceptor responsiveness can independently regulate atrial, ventricular and vascular responses to the α₁-adrenoceptor agonist, phenylephrine. Therefore, these disease states may alter the physiological control of the cardiovascular system by noradrenaline and adrenaline as well as the responsiveness in disease states to therapeutic agents acting via α-adrenoceptors.