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The role of endogenous opioid peptides in physiological and pharmacological reward responses--a survey of present-day knowledge.

Endogenous opioid peptides (EOP) participate in a variety of physiological and pharmacological responses that can be recognized by: increased concentrations of EOP in the cerebrospinal fluid; a combination of euphoria and analgesia; and suppression of the responses by specific opiate antagonists. Application of these responses is exemplified in acupuncture, in self-stimulation via hypothalamic electrodes, and in food and fluid consumption. For example, intake of sweet solutions exerts a biphasic effect: in the beginning pain threshold is elevated, but later on tolerance to morphine-induced analgesia develops. A supply of 2% NaCl also stimulates fluid intake as well as raising the pain threshold. Stress-induced analgesia is due to coupled release of ACTH and beta-endorphin from the pituitary. In man, large variations in pain sensitivity may be related to the level of intrinsic EOP.

Analgesia↗

Ingestive/aversive response of rats to sweet stimuli. Influence of glucose, oil, and casein hydrolyzate gastric loads.

Facial consummatory responses reflecting ingestive and aversive perceptions were studied and quantified in rats chronically implanted with gastric and oral catheters. A gustatory stimulus of 50 microliters of 0.6 mol.l-1 sucrose was injected into the mouth every 5 min during 90 min. At time zero, one of seven loads was injected into the stomach. These consisted of, 5 ml of water, or 5 ml solution containing 1 g glucose, 3 g glucose, 1 g casein hydrolyzate, 3 g casein hydrolyzate, or of oil 0.6 ml, or 1.4 ml. The typical ingestive facial consummatory responses in response to sweet stimuli were observed prior to all gastric loads, and also after the water load. On the other hand, the consummatory responses to sweet stimuli turned aversive after all three high-calorie gastric loads. The magnitude of this decrease in palatability (negative alliesthesia) was similar after glucose, casein hydrolyzate, and oil. The reversal of the consummatory responses from ingestive to aversive did not reach the threshold of statistical significance after the three low-calorie gastric loads. These results would tend to show that the intestinal signal for alimentary alliesthesia is nonspecific.

Animals↗

Taste detection of phytoecdysteroids in larvae of Bombyx mori, Spodoptera littoralis and Ostrinia nubilalis.

A number of plants produce significant amounts of phytoecdysteroids that can disrupt the hormonal levels of insects feeding upon them. Insects equipped with taste receptors sensitive to phytoecdysteroids are able to avoid such plants. How common is this strategy? By recording from the lateral and medial sensilla styloconica in two polyphagous species (Ostrinia nubilalis and Spodoptera littoralis) and in a monophagous species (Bombyx mori), we tested whether the receptors could detect three commonly occurring phytoecdysteroids 20-hydroxyecdysone (20E), ponasterone A (ponA) and ecdysone (E). In B. mori, 20E and ponA elicited dose-dependent responses with a threshold of 1 &mgr;M only in the medial sensilla. In O. nubilalis, 20E, E and ponA elicited responses at threshold of 1 &mgr;M in both sensilla. In S. littoralis, 20E elicited responses with a threshold of 10 &mgr;M in both sensilla. By means of behavioural choice tests, we show that 20E is an effective feeding deterrent for O. nubilalis and S. littoralis first instar larvae. This suggests that the perception of phytoecdysteroids is more common among phytophagous lepidoptera than previously thought, although their toxicity or antifeedancy varies between species.

Journal Article↗

Pimozide does not impair sweetness discrimination.

In an initial experiment pimozide decreased preference for a weak sucrose solution but increased preference for a strong solution on the descending limb of the concentration-intake function. As these effects resemble those of dilution, we therefore investigated whether pimozide decreases the perceived intensity of sweet stimuli. Rats were trained to perform a conditional discrimination in a T-maze. A correct response was rewarded by access to a 10% sucrose solution; an incorrect response was punished by confinement in the non-rewarded arm. In the first part of this experiment the discriminative stimulus, located at the choice point of the T-maze, was either water or sucrose, initially a 10% solution, but reduced gradually to 0.0003%. In the second part of the experiment, the discriminative stimulus was either 1% sucrose or a weaker solution, which was initially 0.0001% then raised gradually to 0.5%. Performance fell below 75% accuracy at 0 versus 0.0012% and at 1% versus 0.1%. Pimozide (0.5 mg/kg) administered at these (and other) levels of difficulty decreased running speed but had no effect on discrimination accuracy. As pimozide did not affect either the threshold for sweetness perception or the discrimination of a just noticeable difference, the decreased responsiveness of neuroleptic-treated rats to sweet rewards cannot be explained by a change in the perception of sweetness.

Animals↗

Orotactile sensation, gustation and palatability: a pilot study.

The hypothesis that deficits in orotactile sensitivity may affect gustation and palatability is not new. It is supported by animal models employing deafferentation; however, little direct evidence supports the application of the model to humans. Indirect evidence comes from four separate fields: (1) neuroanatomy, (2) physiology, (3) developmental biology, and (4) learning theory. The results of a pilot study with humans provide additional direct evidence that implicates the role of orotactile sensitivity in human gustation. In this pilot study, the oral cavity was topically anesthetized to determine whether gustation would be compromised to a similar extent as orotactile sensitivity. The time course of the degree of anesthesia was determined by prior measurements of oral-tactile sensitivity using an oral air-based aesthesiometer. Different concentrations of NaCl-solution were presented to subjects in order to determine gustatory thresholds before and after anesthesia. Analysis of magnitude-estimation data indicated that there were statistically significant decreases in gustatory sensitivity after anesthesia. Basic and applied implications of this area of research are discussed.

Adult↗

Isolation, structure determination, synthesis, and sensory activity of N-phenylpropenoyl-L-amino acids from cocoa (Theobroma cacao).

Application of chromatographic separation and taste dilution analyses recently revealed besides procyanidins a series of N-phenylpropenoyl amino acids as the key contributors to the astringent taste of nonfermented cocoa beans as well as roasted cocoa nibs. Because these amides have as yet not been reported as key taste compounds, this paper presents the isolation, structure determination, and sensory activity of these amino acid amides. Besides the previously reported (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine (clovamide), (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-tyrosine (deoxyclovamide), and (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-tyrosine, seven additional amides, namely, (+)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-aspartic acid, (+)-N-[4'-hydroxy-(E)-cinnamoyl]-L-aspartic acid, (-)-N-[3',4'-dihydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-L-glutamic acid, (-)-N-[4'-hydroxy-(E)-cinnamoyl]-3-hydroxy-L-tyrosine, (+)-N-[4'-hydroxy-3'-methoxy-(E)-cinnamoyl]-L-aspartic acid, and (+)-N-[(E)-cinnamoyl]-L-aspartic acid, were identified for the first time in cocoa products by means of LC-MS/MS, 1D/2D-NMR, UV-vis, CD spectroscopy, and polarimetry, as well as independent enantiopure synthesis. Using the recently developed half-tongue test, human recognition thresholds for the astringent and mouth-drying oral sensation were determined to be between 26 and 220 micromol/L (water) depending on the amino acid moiety. In addition, exposure to light rapidly converted these [E]-configured N-phenylpropenoyl amino acids into the corresponding [Z]-isomers, thus indicating that analysis of these compounds in food and plant materials needs to be performed very carefully in the absence of light to prevent artifact formation.

Amides↗

Sensory and physiologic effects of menthol and non-menthol cigarettes with differing nicotine delivery.

Many smokers choose menthol-flavored cigarettes, however, the influence of menthol on the effects of smoke-delivered nicotine is unknown. Research and commercial cigarettes, menthol and non-menthol, that delivered a wide range of nicotine were evaluated. Menthol (n=18) and non-menthol (n=18) cigarette smokers participated in a single session during which three cigarettes were smoked 45 min apart, in random order. Federal Trade Commission (FTC) nicotine yields of the three cigarettes were: research, low yield, 0.2 mg, commercial cigarettes (average), 1.2 mg; research, high yield, 2.5 mg. Commercial and high-yield cigarettes increased heart rate (HR) and blood pressure more than low-yield cigarettes; although, no differences in exhaled carbon monoxide (CO) occurred. Participants smoked commercial cigarettes faster and with fewer puffs than either of the research cigarette indicating production differences can affect topography. There was a significant group by cigarette interaction on satisfaction, and relief from cigarette craving. High-yield non-menthol cigarettes reduced craving and were rated as more satisfying than high-yield menthol cigarettes. No differences between menthol and non-menthol cigarettes on other subjective measures (strength, psychological reward, negative effects) were observed. Our findings indicate that nicotine delivery, but not mentholation, influences cardiovascular and most subjective measures. These results illustrate the importance of threshold levels of nicotine on subjective responses to cigarette smoking.

Adult↗

Membrane properties of glossopharyngeal sensory neurons in the petrosal ganglion of the cat.

The active and passive properties of petrosal ganglion sensory neurons with axons in the glossopharyngeal nerve were examined with intracellular microelectrodes in an in vitro preparation. Glossopharyngeal neurons could be classified into two groups: H-cells showing an inflexion or hump on the falling phase of the spike and F-cells, generating a short action potential without a hump. Most of the neurons found (85%) were H-cells. The axonal conduction velocity of both types of cells fell into the A delta range, although the average value for F-cells (13 m/s) was higher than that found for H-cells (10 m/s). H- and F-cells had similar resting membrane potentials and input resistances, but different action potential characteristics. F-cells showed a smaller action potential with a faster rate of depolarization, followed by a shorter after-hyperpolarization. The response to depolarizing current pulses applied through the microelectrode was also different in both types of cells. About half of the H-cells could not be depolarized to threshold while 85% of F-cells generated spikes. It is concluded that two different populations of petrosal ganglion neurons send axons into the glossopharyngeal nerve.

Action Potentials↗

Night-time melatonin secretion and seasonally delayed puberty in gilts.

This study was conducted to determine whether the seasonal delay in puberty in autumn is driven by individual differences in night-time melatonin secretion in domestic gilts at the attainment of puberty. A group of spring-born gilts (n = 30) were expected to reach puberty in autumn by the age of 7 months. Eighteen of these gilts were selected in pairs on the basis of matched days of birth. By the expected time, half of the animals showed oestrous symptoms (group CYCLING, n = 9) with the rest remaining silent (group SILENT, n = 9). Afterwards, all gilts were fitted with indwelling jugular catheters for frequent blood sampling. Blood samples were collected from all animals three times during the day followed by three times in the night at 2-h intervals for 48 h. The samples were analysed by a commercial radioimmunoassay (RIA). The results show a consistent 25-fold rise (on average) in night-time melatonin concentration in every animal sampled with group averages ranging from 0.28 +/- 0.04 to 0.37 +/- 0.06 pg/ml at day and from 10.20 +/- 2.16 to 10.67 +/- 0.05 pg/ml at night. Night-time group mean values between CYCLING and SILENT gilts did not differ significantly (10.26 +/- 0.67 and 10.38 +/- 0.94 for the CYCLING; 10.67 +/- 0.05 and 10.20 +/- 2.16 for the SILENT). When 10 pg/ml was used as a threshold value, six individuals did not reach it during the night (low responders). Two of these gilts were CYCLING and four were SILENT. In conclusion, the results presented imply no involvement of the level of night-time melatonin concentration in the seasonal delay of puberty in gilts.

Animals↗

Preparation of antimicrobial compounds by hydrolysis of oleuropein from green olives.

Oleuropein, an intensely bitter glucoside, was isolated from green olives. Hydrolysis products obtained from oleuropein in sufficient quantity for further tests were: (i) beta-3,4-dihydroxyphenylethyl alcohol prepared by acid hydrolysis of oleuropein; (ii) elenolic acid obtained by methanolysis of oleuropein, isolation of the intermediate acetal, and subsequent acid hydrolysis; and (iii) oleuropein aglycone formed by the action of beta-glucosidase on the parent glucoside. Mass spectral verification of the isolated compounds and ultraviolet absorption data are given. Oleuropein and its aglycone had similar threshold levels for detection of bitterness, whereas elenolic acid and beta-3,4-dihydroxyphenylethyl alcohol were not judged to be bitter.

Anti-Infective Agents↗

Odorous products of the chlorination of phenylalanine in water: formation, evolution, and quantification.

To explain some of the possible origins of an odor episode which took place in a drinking water supply in the region of Paris (France), the chlorination reaction in water of phenylalanine was studied. This amino acid was chosen for first experiments because of its physical and chemical particular properties. Changes in the different byproducts formed were followed by high-performance liquid chromatography (HPLC) over a period of time. N-chlorophenylalanine (mono-N-chlorinated amino acid) and then phenylacetaldehyde were the major products formed for the lower chlorine to nitrogen molar ratios. For Cl/N molar ratios of 1 and beyond, phenylacetonitrile and N-chlorophenylacetaldimine appeared and increased with the chlorination level. N-chlorophenylacetaldimine was quantified by using its difference of stability in various organic solvents. Our attention was first directed to the monochlorinated derivative but further examination indicated that it could not be responsible for odor troubles: it dissociated before reaching the consumer's tap and it was produced at consistently low yields under conditions relevant to drinking water treatment. On the contrary, chloroaldimine appeared to be a very odorous and water-stable product: it strongly smells of swimming pool with a floral background. The odor detection threshold is about 3 microg x L(-1) and it can persist for more than one week at 18 degrees C. It is now suspected of being a source of off-flavor concerns among consumers.

Acetonitriles↗

Capsaicin activated currents in rat dorsal root ganglion cells.

Capsaicin is a pungent-tasting compound produced by plants in the Capsium family that activates a subset of primary afferent neurons associated with pain and thermoreception. Previous studies from dorsal root ganglion (DRGs) neurons suggest that many of capsaicin's physiological responses are a consequence of its activating a cation-selective current. To further characterize the responses to capsaicin whole-cell patch-clamp measurements were performed on rat DRGs to which 0.1-10 microM capsaicin was continuously applied. The capsaicin-activated currents exhibited marked variability in their thresholds, amplitude (to 15 nA), rates of desensitization, and the number of distinct maxima in the evoked current. Similar responses were found in rat trigeminal ganglion cells. The heterogeneity in the magnitude of the currents evoked by 0.1 microM capsaicin likely reflects different types of capsaicin-sensitive neurons; a result consistent with in vitro extracellular recordings from capsaicin-sensitive sensory afferents (Seno and Dray 1993).

Animals↗

The photophase light intensity does not affect the scotophase melatonin response in the domestic pig.

This study investigated the effects of the photophase light intensity on the scotophase melatonin response. Twelve, 8-month-old crossbred gilts were allocated to three groups of four and housed in temperature- and lighting-controlled climate rooms. The rooms had a light intensity of 40, 200 or 10,000 lx and a light-dark cycle of 12 L:12 D. The gilts were allowed to acclimatize to a new lighting regimen for 1 week before being sampled at 2h intervals for 24h. Following the sampling, pigs were transferred under a different light intensity, allowed to adjust for 1 week and sampled again. The procedure was repeated three times so that all the groups went through all three lighting regimens (light intensities). All the gilts exhibited a clear circadian serum melatonin rhythm under each lighting regimen with high melatonin concentrations occurring during the scotophase. There was no difference in the scotophase melatonin response in terms of mean concentrations or duration of increased melatonin levels within or between the groups under different lighting regimens. There was considerable inter-individual variation in the dark phase melatonin response but the individual profiles were consistent under the different lighting regimens. It is concluded that when a certain threshold light intensity (<40lx) is exceeded, the photophase light intensity has no effect on the scotophase melatonin response. These results imply that extremely high light intensities during the photophase would provide no additional benefits compared with normal comfortable light intensity, if artificial lighting programs were introduced to commercial piggeries in order to reduce seasonal effects on reproduction.

Animals↗

Three Drosophila mutations that block associative learning also affect habituation and sensitization.

Drosophila melanogaster has been cultured with shock to avoid various odors. Mutants that failed to learn this task have been isolated. Here we report tests on these mutants for more elementary types of behavioral plasticity--habituation and sensitization of a reflex. Fruit flies have taste receptors on their feet. When a starved, water-satiated fly has sucrose applied to one foot, it usually responds by extending its proboscis. In normal flies this feeding reflex shows habituation: application of sugar to one foot depresses responsiveness through the contralateral leg for at least 10 min. The reflex also shows brief sensitization application of concentrated sucrose solution to the proboscis increases subsequent responsiveness to tarsal stimulation for 2-5 min. In three associative learning mutants , the proboscis-extension reflex is present with a normal threshold but behavioral modulation of the response is altered. The dunce, turnip, and rutabaga mutants all habituate less than normal flies. In addition, sensitization wanes unusually rapidly in dunce and rutabaga flies, lasting less than a minute in the case of dunce.

Animals↗

Olfactory cleft disease: an analysis of 13 cases.

OBJECTIVES: Olfactory cleft disease was defined as (1) an olfactory disability related with a clinical and/or radiologic abnormality of the olfactory cleft and (2) a pathologic process limited to or predominating in the olfactory cleft. The objectives of this study were to describe the clinical and radiologic findings of this entity and to report the effect of medical therapy on the sense of smell. STUDY DESIGN AND SETTING: Thirteen patients with the criteria of olfactory cleft disease were included in this retrospective study. All patients had bilateral olfactory cleft abnormalities. A complete ENT examination with endoscopic evaluation and a computed tomography scan were performed in all cases. An olfactory threshold test was available in 12 cases before and after medical therapy, which included oral and topically administered steroid therapy. RESULTS: Olfactory disability was the major symptom of olfactory cleft disease. Other symptoms of chronic rhinosinus dysfunction was present in 75% of cases. Three pathologic processes were identified in patients with olfactory cleft disease: malformative, inflammatory, and inflammatory associated with anatomical deformities of olfactory cleft boundaries. Medical therapy was effective in lowering olfactory thresholds in 25% of the cases. CONCLUSIONS AND SIGNIFICANCE: Olfactory cleft disease involves various pathophysiologic processes. Computed tomography scanning provides the most information for diagnosis. Indications of functional endoscopic surgery remain to be defined after failure of medical therapy.

Adolescent↗

Different food sources affect the gustatory response of Anaphes iole, an egg parasitoid of Lygus Spp.

The gustatory response of female Anaphes iole wasps to naturally occurring carbohydrates, a commercial food source, and host (Lygus lineolaris) frass was determined. Wasps responded to all 14 of the sugars at the highest concentration tested (2 M). At this concentration, sucrose, glucose, maltose, melezitose, fructose, and erlose all elicited > 90% acceptance. The lowest concentration that evoked a response (= acceptance threshold) for these sugars was < 1/256 M, with the exception of glucose. which was 1/16 M. Raffinose, trehalose, mannose, galactose, melibiose, rhamnose, stachyose, and lactose led to < 50% gustatory response by the wasps at 2 M, and were categorized as "moderately stimulatory sugars." The acceptance threshold for these sugars was > 1/4 M, with the exception of raffinose, which was 1/256 M. In trials with moderately stimulatory sugars combined with either sucrose or maltose, only the rhamnose+maltose mixture significantly inhibited the gustatory response of A. iole. Food and water deprived parasitoids readily accepted the moderately stimulatory sugars. Eliminade, a commercial food supplement, was readily accepted (92%) by A. iole. Conversely, the wasps did not feed on host frass. Chemical analysis of L. lineolaris frass demonstrated the presence of glucose, sucrose, fructose, trehalulose, and melezitose, apparently at concentrations below those perceived by A. iole. The latter two compounds were previously known only from homopteran honeydew (trehalulose and melezitose) and bacteria (trehalulose). With respect to gustatory response to nectar and honeydew sugars, A. iole differs markedly from other hymenopterans that have been studied in that this parsitoid accepted all the naturally occurring sugars with which it was tested. Moreover, this parasitoid had lower acceptance thresholds than other hymenopterans for many of the sugars. This broad and sensitive range of gustatory perception might be helpful in the development of a food source for the wasp that is not exploited by the host.

Animal Feed↗

Calcium deficiency alters chorda tympani nerve responses to oral calcium chloride.

As a preliminary examination of the influence of calcium deficiency on gustatory sensitivity to calcium, we recorded electrophysiological responses of the chorda tympani nerve of calcium-replete and calcium-deprived rats. Relative to rats fed calcium-replete diet, rats fed low calcium diet had lower electrophysiological response thresholds to CaCl2 (300 vs. 30 microM) and calcium lactate (300 vs. 100 microM) but not NaCl. The calcium-deprived animals had a greater chorda tympani response to 30, 100 and 300 microM CaCl2 and 30 and 100 microM calcium lactate but a smaller chorda tympani response to 30, 100 and 300 mM CaCl2 and to 100 mM MgCl2. A behavioral study using an ascending series of 48-h two-bottle preference tests showed that the threshold for acceptance of CaCl2 was similar to the electrophysiological threshold (310 microM in replete rats, 100 microM in calcium-deprived rats). These findings raise the possibility that changes in calcium status influence the perception of calcium, which, in turn, influences calcium intake.

Animals↗

Signalling the state of the digestive tract.

The gastrointestinal tract has a rich sensory innervation. Extrinsic afferents in vagal, splanchnic and pelvic nerves project to the CNS where gut reflex function is coordinated and integrated with behavioural responses (e.g. regulation of food intake) and mediate sensations. The afferent information conveyed by vagal and spinal mechanosensitive afferents can be very different. Vagal afferents have low thresholds of activation and reach maximal responses within physiological levels of distension. In contrast, spinal afferents, although many have corresponding thresholds for activation, are able to respond beyond the physiological range and encode both physiological and noxious levels of stimulation. However, mechanosensitivity is not fixed but can be influenced by a wide range of chemical mediators released as a consequence of ischemia, injury and inflammation. Indeed, previously mechanical insensitive afferents can develop mechanosensitivity during inflammation and a variety of chemical mediators are implicated in this sensitisation process. Chemosensitivity is also a property of vagal mucosal afferents that detect the chemical milieu for chemicals absorbed across the epithelium or released from enteroendocrine cells that are strategically positioned to "taste" luminal contents. Thus, there exists a complex interplay between immunomodulators, neurotransmitters and neuroendocrine factors that underlie gastrointestinal sensing mechanisms and enable orchestration of appropriate host responses.

Animals↗