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Activating action tendencies: The influence of action priming on alcohol consumption among male hazardous drinkers.

OBJECTIVE: Despite the importance of action components in information processing models of substance-use motivation, there has been relatively little research that has specifically examined the effects of behavioral cues on motivation to use alcohol. The current study examined the effects of action priming on alcohol-use motivation. METHOD: One hundred and eighty-eight hazardous drinkers completed a cue-exposure procedure followed by a beer-tasting task. Participants were exposed to their preferred alcohol beverage while they either lifted the beverage (action prime) or leaned toward the beverage (control). Following alcohol-cue exposure, participants completed a taste-test procedure in which they sampled three glasses of beer. Urges to drink following cue exposure and volume of beer consumed during the taste test were the primary dependent variables. RESULTS: Ratings of urge to drink increased in both prime conditions following alcohol-cue exposure and predicted the amount of beer consumed. The priming conditions did not differentially influence urge; however, there was a significant Prime x Gender interaction for volume of beer consumed. Men in the action-prime condition consumed more alcohol in the subsequent taste-test procedure than men who were in the control condition. CONCLUSIONS: These results suggest that behavioral sequences associated with drinking may prime alcohol-related motivational states among hazardous-drinking men. Moreover, these action primes may affect subsequent alcohol use independent of changes in subjective indices of alcohol-related motivation. Implications for understanding the distinct effects of alcohol-related cues on controlled and automatic processes underlying alcohol use are discussed.

Adult↗

Diet and liver disease--a glimpse into the future.

The complex interaction between liver disease and food intake is not well defined. There are two aspects to consider: how liver disease affects food intake and whether or not diet can affect liver disease. Acute and chronic liver disease have been shown to influence taste, smell, food preference, and appetite. The liver may also play a role in food selection through reflex pathways. Intake of various macronutrients can alter serum liver enzymes and bilirubin without necessarily being associated with changes in pre-existing liver disease. Nonetheless, there is evidence that diet can be associated with both adverse and beneficial changes in outcome in animal models and patients with liver disease. These issues are difficult to unravel; however, there is potential for significant clinical advances from examining this area.

Diet↗

Differential alcohol drinking behaviour and dependence in the Naples low- and high-excitability rat lines.

Alcoholism is composed of a series of phenomena, which can be approached in model systems. Our aim was to investigate psychogenetics of alcohol drinking behaviour and dependence in the Naples rat lines. Thus, adult male rats of the Naples low- (NLE), high-excitability (NHE) and random-bred control (NRB) lines had 24-h access to a four-bottle system with tap water and 5, 10 and 20% alcohol solutions. Total voluntary alcohol intake and preference were measured during a 6-week period. In order to analyze behavioural dependence, two abstinence periods were introduced, followed by re-exposure to the bottles. The first was a pure re-test and the second was a quinine test (adding 0.02% quinine alcohol solution). Finally, to verify the role of opioids on alcohol drinking behaviour, rats received naltrexone (5 mg/kg i.p.). Thirty minutes later, they had access for 2 h to a three-bottle system with water, 5 and 20% alcohol solution, respectively. Results indicate that (i) total alcohol intake on day 1 was higher in both NLE/NHE, becoming higher in NLE rats during the 6-week period, (ii) different alcohol preference patterns in the Naples lines were observed over time of testing, (iii) during re-test, NLE rats showed neither reversibility nor alcohol deprivation effect, (iv) during quinine test, only NLE rats reduced alcohol intake to a lower extent and (v) naltrexone reduced by 50% the intake of the preferred solution. Therefore, the NLE rats appear as a new model for studying the neural substrates of the dependence behaviour.

Alcohol Drinking↗

Probing the sweet determinants of brazzein: wild-type brazzein and a tasteless variant, brazzein-ins(R18a-I18b), exhibit different pH-dependent NMR chemical shifts.

Brazzein is a small, intensely sweet protein. As a probe of the functional properties of its solvent-exposed loop, two residues (Arg-Ile) were inserted between Leu18 and Ala19 of brazzein. Psychophysical testing demonstrated that this mutant is totally tasteless. NMR chemical shift mapping of differences between this mutant and brazzein indicated that residues affected by the insertion are localized to the mutated loop, the region of the single alpha-helix, and around the Cys16-Cys37 disulfide bond. Residues unaffected by this mutation included those near the C-terminus and in the loop connecting the alpha-helix and the second beta-strand. In particular, several residues of brazzein previously shown to be essential for its sweetness (His31, Arg33, Glu41, Arg43, Asp50, and Tyr54) exhibited negligible chemical shift changes. Moreover, the pH dependence of the chemical shifts of His31, Glu41, Asp50, and Tyr54 were unaltered by the insertion. The insertion led to large chemical shift and pKa perturbation of Glu36, a residue shown previously to be important for brazzein's sweetness. These results serve to refine the known sweetness determinants of brazzein and lend further support to the idea that the protein interacts with a sweet-taste receptor through a multi-site interaction mechanism, as has been postulated for brazzein and other sweet proteins (monellin and thaumatin).

Genetic Variation↗

Microvascular fin-like structure of the foliate papillae of the rabbit tongue using scanning electron microscopic specimens.

Although many morphological studies have been undertaken on the lingual papillae of the rabbit tongue, relatively few have dealt with the microvascular structure and classification of the foliate papillae (FoP) by means of microvascular cast specimens (MVCS) and using scanning electron microscopy (SEM). For the present study, a three dimensional observation and classification was carried out by SEM. The morphological characteristics of the outer frame structure were observed by means of MVCS of FoP which were located on both posteroperipheral parts of the tongue. They showed a bead-like appearance and consisted of 14-18 transverse and slightly bent fin-like structures, running from the dorsal surface to both peripheral sides symmetrically. These are effectively increased on the surface areas and play the functional role of receiving the taste sense. FoPs can be classified into three types: type I (14 fins), type II (16 fins), type III (18 fins) according to the fin numbers.

Animals↗

Sex and sugar in yeast: two distinct GPCR systems.

Although eukaryotic G-protein coupled receptor (GPCR) systems are well known for their ability to detect and mediate rapid responses to extracellular signals, the full range of stimuli to which they respond may not yet have been identified. Activation of GPCRs by hormones, pheromones, odorants, neurotransmitters, light and different taste compounds is well established. However, the recent discovery of a glucose-sensing GPCR system in Saccharomyces cerevisiae has unexpectedly added common nutrients to this list of stimuli. This GPCR system mediates glucose activation of adenylate cyclase during the switch from respirative/gluconeogenic metabolism to fermentation. The GPCR system involved in pheromone signalling in S. cerevisiae has already served as an important model and tool for the study of GPCR systems in higher eukaryotic cell types. Here, we highlight the similarities and differences between these two signalling systems. We also indicate how the new glucose-sensing system can serve as a model for GPCR function and as a tool with which to screen for heterologous components of signalling pathways as well as for novel ligands in high-throughput assays.

Amino Acid Sequence↗

Sensitization to amphetamine, but not phencyclidine, disrupts prepulse inhibition and latent inhibition.

RATIONALE: Schizophrenia has been linked to dysregulation of dopamine and glutamate transmitter systems. Attempts to model aspects of schizophrenia in animals have made use of treatments that primarily affect dopaminergic (e.g., amphetamine, Amp) and glutamatergic (e.g., phencyclidine, PCP) function. In addition to exerting short-term acute effects, these agents also induce long-term effects, as seen, for example, in neurochemical and behavioural sensitization. OBJECTIVES: The goal of this work was to compare Amp- and PCP-sensitized states on two measures of information processing that are impaired in schizophrenia, prepulse inhibition (PPI) of the acoustic startle reflex and latent inhibition (LI). METHODS: Rats received injections of Amp, PCP or saline 3 days per week for 3 weeks. The Amp dose increased from 1 to 3 mg/kg, at the rate of 1 mg/kg each week. The PCP dose was 3 mg/kg throughout. After various periods of withdrawal rats were tested for PPI and LI. RESULTS: Repeated intermittent treatment with Amp or PCP resulted in augmented locomotor responses to challenge with each drug, providing an operational index that sensitization had occurred. Rats sensitized to Amp showed disrupted PPI when tested drug free at 3, 21 and 60 days of withdrawal. Amp-sensitized rats also showed abolition of the LI effect. Rats sensitized to PCP did not show deficits in any of these behaviours when tested drug free. CONCLUSIONS: Because disrupted PPI and LI have both been reported in schizophrenic patients, these results suggest that the Amp-sensitized state may represent a useful model for investigating the neural bases of information processing deficits in schizophrenia.

Amphetamine↗

"Depression" increases "craving" for sweet rewards in animal and human models of depression and craving.

This study consisted of two experiments, one in rats and one in human volunteers, that used the identical progressive ratio (PR) operant procedure. In both experiments, responding was reinforced under a progressively increasing work requirement, and different groups of subjects received reinforcers that varied in sweetness. In experiment 1, rats were subjected to chronic mild stress, a well-validated animal model of depression. Performance under the PR schedule increased in subjects reinforced with conventional precision pellets (which contain 10% sucrose) or very sweet pellets, but not in subjects reinforced with sugar-free pellets. In experiment 2, volunteers were subjected to a depressive musical mood induction. Performance under the PR schedule increased in subjects reinforced with chocolate buttons, but not in subjects reinforced with with buttons made from the relatively unpalatable chocolate substitute carob. In experiment 2, depressive mood induction also increased chocolate craving, as measured by a novel questionnaire, and there were significant correlations between chocolate craving and chocolate-reinforced PR performance. These results suggest that performance under the PR schedule provides a measure of craving rather than reward, and that craving for sweet rewards is increased by depressive mood induction in both animal and human models. Implications for the interpretation of pharmacological studies using the PR procedure are also discussed.

Adult↗

Novel aspects of signaling and ion-homeostasis regulation in immunocytes. The TRPM ion channels and their potential role in modulating the immune response.

In just a few years, the discovery and subsequent characterization of several members of the TRPM family of cation channels have provided us with surprising new insights into unknown aspects of cellular ion-homeostasis regulation. This includes reports about ADP-ribose functioning as a novel intracellular second messenger and gating molecule of the Ca(2+)-permeable TRPM2 channel, studies demonstrating the central role of mouse TRPM5 in taste signaling, as well as the unexpected involvement of TRPM6 and TRPM7 in regulating Mg(2+)-homeostasis, or the cool properties of TRPM8 acting as a cold and menthol sensor in sensory neurons. At least four of the eight known TRPM proteins have been shown to be present in the immune context: TRPM1 (melastatin), TRPM2, TRPM4 and TRPM7. Although we currently lack animal models allowing a detailed assessment of the potential involvement of TRPM family members in modulating the immune response, the powerful combination of molecular and cellular biology, biochemistry, and electrophysiology have provided the first clues as to how these molecules could contribute to immunity.

Animals↗

Gastrointestinal regulation of food intake.

Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste-like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes.

Adipose Tissue↗

Rat as model for studying behavior effects of hCG.

The demonstration of receptors for luteinizing hormone (LH)/human chorionic gonadotropin (hCG) in several parts of rat brain suggested their novel functional role. Subsequent studies tested the effect of hCG (intraperitoneally or intracerebroventricularly) on brain arousal and different types of stress situations in an intact female rat model on the day of proestrus. Treatment resulted in changes of activity and several other behavioral patterns associated with sites of brain hCG/LH receptors. hCG given peripherally caused a longer sleeping time and a decreased activity level. Whereas administration of indomethacin alone had no effect, coadministration inhibited the effects of hCG. hCG increased immunoreactive prostaglandin D2 (PGD2) and decreased PGE2 in brain areas controlling activity and sleep. hCG effects were probably mediated via prostaglandin pathways. After central hCG treatment, animals were less active and showed less exploratory behavior in an open-field box than the control animals. Taste and odor neophobias were dramatically decreased following central injection of hCG. hCG-treated rats were less anxious and exhibited a higher level of maternal interest than the controls. hCG treatment also had a beneficial effect against stress ulcer, which was prevented by pretreatment with antisense receptor oligonucleotide, suggesting a direct hCG receptor-mediated effect. In summary, because hCG can cross the blood-brain barrier, both peripheral administration and central administration affect several behavioral patterns. This effect is similar to treatment with anxiolytics and suggests the functional relevance of brain LH/hCG receptors. Some observed behavioral changes have parallels in pregnant women.

Animals↗

Conditioned alcohol-like and alcohol-opposite responses in humans.

Conditioned heart rate and skin temperature responses of 12 social drinkers were observed following repeated exposure to alcohol. Each subject received alcohol for four sessions in one room and a non-alcoholic drink for four sessions in a room of quite different appearance. Alcoholic and non-alcoholic drinks were distinctive and the alcoholic content could not be determined on the basis of taste. In the final three testing sessions, placebos were presented in order to test the influence of room and drink cues separately and in combination. A conditioned heart rate response opposite in direction to the alcohol effect was elicited by room and drink cues in combination and by the room cue in isolation. These results were in accordance with the predictions of the conditioning model of tolerance. A conditioned heart rate response in the same direction as the drug effect was elicited by the drink cue presented in isolation. Similar, but non-significant changes were also obtained with skin temperature. In addition, conditioned responses occurred independently of any expectancy. The results demonstrated that the direction of conditioned drug responses may depend on the type of stimulus presented.

Adult↗

Reward and anxiety in genetic animal models of childhood depression.

One of the most important criteria for major depressive disorder in adults and in children and adolescents as well, is the loss of interest in or pleasure from typically enjoyable experiences or activities: anhedonia. Anxiety is frequently co-morbid with depression. We examined reward and anxiety in genetic animal models of childhood depression. Two different "depressed" lines were studied: the Flinders Sensitive Line (FSL) and their controls, Sprague-Dawley (SD) rats and the Wistar Kyoto (WKY) line and their controls, Wistar rats. Recently, we found that prepubertal rats (about 35 days old) from these lines exhibited increased immobility in the swim test, and abnormal social play observed after 24-h isolation. We hypothesized that FSL and WKY prepubertal rats will further show anhedonia in two different behavioral assays: the conditioned place preference test (CPP), examining the rewarding aspect of social interaction and the saccharin preference test. Behavior in the open field paradigm and freezing behavior in the CPP apparatus were also used as measures of anxiety. WKY, but not FSL prepubertal rats, consumed less of the saccharin solution compared to their control line. FSL, and WKY prepubertal rats found social interaction to be rewarding to a similar extent as their control lines, in the CPP test. Only the WKY rats showed anxiety in behavior in the open field and freezing behavior in the CPP paradigm. The results suggest that WKY prepubertal rats are anxious and sensitive to stress-induced anhedonia, while FSL prepubertal rats exhibit none of these symptoms.

Age Factors↗

Chemometrical classification of pumpkin seed oils using UV-Vis, NIR and FTIR spectra.

The main outcome of this work is elaboration of classification models for edible oil samples representing the most widespread brands of Austrian pumpkin seed oil. A complete spectral characterisation of the pumpkin seed oil samples by UV-Vis, NIR and FTIR spectra was obtained together with their basic sensorial classification. Chemometrical processing of the measured data enabled the detection of the most important spectral features, which are crucial for categorising the oils into two or three classes according to their sensory quality evaluated by a panel of experts. The elaborated models thus make it possible to predict the category into which a hitherto unclassified oil sample belongs--considering classification into either two categories, containing oils with overall acceptable scores or oils that were not accepted, or three categories, involving oils fulfilling all quality criteria, oils with good scores and not accepted oils. This will perspectively facilitate the determination of chemical substances responsible for bad taste, odour and colour of the respective oil brands, as well as finding substances contributing to the excellent sensorial perception of some tested products.

Algorithms↗

Interoceptive and integrative contributions of forebrain and brainstem to energy balance control.

An anatomically distributed model of energy balance control contrasts with the widely held hypothalamic center model. The distributionist model is recommended by the observations that the caudal brainstem contains critical interoceptive, integrative and neurochemical mediating functions. A prominent example of interoceptive function is sensitivity to the adipose tissue-derived hormone, leptin. To complement the well established focus on hypothalamic leptin receptors (Ob-Rb), we describe an extensive distribution of Ob-Rb in the brainstem. These receptors, moreover, are functionally relevant given the intake suppressive effects of fourth-intracerebroventricular (i.c.v) and brainstem intraparenchymal (in dorsal vagal complex) delivery. A wide variety of intake relevant peptides receptors are found in hypothalamus, but these receptors are also widely distributed in the caudal brainstem. As an example of the functional relevance of these neurochemical mediators, we describe ingestive effects of ligands for melanocortin 3/4 and corticotrophin-releasing hormone receptors obtained with brainstem ventricular and parenchymal (dorsal vagal complex and parabrachial nucleus) delivery. It is clear that responses obtained from hypothalamic treatments can arise independently from stimulation of caudal brainstem receptors. We have used the chronic decerebrate preparation to ask whether the brainstem contains integrative substrates sufficient to mediate behavioral responses to variations in physiological state. The experiments reveal that the brainstem is indeed sufficient for the integration of taste and gastrointestinal signals that co-determine the size of meals in the short term. Decerebrate rats, however, do not respond to food deprivation or to reductions in the number of daily feeding opportunities. These results suggest that the brainstem in neural isolation from forebrain influence is not sufficient for ingestive response to systemic/metabolic signals that affect intake over the long term. The relative contribution of brainstem and forebrain substrates to long-term intake and body weight control in the neurologically intact animal, remains unclear. The data reviewed support a distributed anatomical model of energy balance and recommend increased attention to specific responses (behavioral, autonomic and endocrine) that are mediated by local (brainstem or forebrain) interoceptive and integrative processes, and those requiring bi-directional interactions.

Animals↗

Conditioned gaping in rats: a selective measure of nausea.

When intraorally infused with a flavored solution previously paired with an emetic drug, rats display a characteristic gaping reaction that reflects conditioned nausea in this species that is unable to vomit. The commonly used conditioned taste avoidance measure, is not a selective measure of nausea because nearly every drug tested (even rewarding drugs) is capable of producing a conditioned taste avoidance. In contrast, only emetic drugs produce conditioned gaping reactions in rats, and anti-emetic drugs interfere with the establishment and the expression of conditioned gaping reactions but do not interfere with conditioned taste avoidance. The conditioned gaping reaction can be used as a pre-clinical tool to evaluate the side effects of nausea that might result from newly developed pharmaceutical agents.

Animals↗

Chemometric analysis of Ragusano cheese flavor.

Ragusano cheeses were produced in duplicate from milk collected from pasture-fed and total mixed ration (TMR)-fed cattle at four time intervals. The cheeses were subjected to chemical analysis, conventional sensory testing, and gas chromatography-olfactometry (GCO). Data from each type of analysis were examined by principal component and factor analysis and by pattern recognition (SIMCA) to see if sufficient information for classification into pasture-fed and TMR-fed groups was contained therein. The results clearly indicate that there are significant differences in sensory panel and chemical analysis results between the two cheeses. The data were also examined to see if models of sensory responses as a function of analytical or GCO results or both could be constructed with the modeling technique partial least-squares regression (PLS). Strong PLS models of some sensory responses (green and toasted odor; salt, pungent, bitter, and butyric sensations; and smooth consistency) were obtained.

Animal Feed↗

Astringent subqualities in acids.

Astringency, astringent subqualities (drying, roughing and puckering) and sourness were compared among six acids: hydrochloric, lactic, citric, acetic, fumaric and malic acids. The attribute profiles of organic acids were similar to each other but different from hydrochloric acid, the only inorganic acid, which was the most astringent and the least sour. In a second experiment, two inorganic acids (hydrochloric and phosphoric) and two organic acids (citric and malic) were tested at three concentration levels. At approximately equal levels of overall sensory impact, the inorganic acids were alike in astringency and sourness, receiving higher ratings for roughing and drying, and lower ratings for sourness than the organic acids. Interactions with concentration (differences in psychophysical functions) for the subquality of drying were noted, in addition to the differences in the astringent subqualities of roughing and drying seen across acids in both experiments. The higher level of astringency for inorganic acids suggests that the current model for tannin binding to salivary proteins as an explanation of astringency needs to be extended to include a direct pH-dependent effect.

Adult↗