Stimulus generalization of conditioned fear in rats over time: olfactory cues and adrenal activity.
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OBJECTIVES: Terbinafine (Lamisil), a widely prescribed oral antifungal agent, reportedly induces taste loss in 0.6% to 2.8% of those taking the drug. However, many so-called taste problems reflect olfactory problems, and the sole empirical study published on this topic, based on whole-mouth testing of a single subject, found no terbinafine-related deficit. In this study, we quantitatively assessed, using well-validated taste and smell tests, chemosensory function in six patients complaining of taste disturbance after terbinafine treatment and compared their test scores to those of six age-, race-, and sex-matched normal controls. METHODS: Taste function was measured using a 96-trial regional test that assesses sweet, sour, bitter, and salty taste perception within the anterior (cranial nerve [CN] VII) and posterior (CN IX) lingual taste bud fields. Smell function was bilaterally evaluated using the 40-item University of Pennsylvania Smell Identification Test. RESULTS: Taste function for sweet-, sour-, and bitter-tasting stimuli was significantly depressed in both the anterior and posterior lingual regions. For sodium chloride, the decrements were confined to the posterior region. Olfactory function was within normal limits. CONCLUSION: These findings 1) support anecdotal case reports of taste loss after terbinafine use, 2) demonstrate that all four major taste qualities are affected, and 3) suggest that olfactory dysfunction is not involved. Because self-report markedly underestimates chemosensory deficits, more extensive quantitative testing of patients receiving terbinafine will likely reveal a much higher prevalence of terbinafine-induced taste loss than currently reported. Since being older than 65 years of age and having a low body mass index are reportedly risk factors for terbinafine-induced taste loss, physicians should be particularly on the alert for elderly persons taking this medication who may become depressed or alter their food intake in response to decreased taste sensation.
Pharmacological studies suggest that increases and decreases in dopamine levels in the nucleus accumbens contribute to positive and negative affective states, respectively. In vivo neurochemical investigations have led to contradictory conclusions, since increases and decreases in dopamine release have been observed in aversive situations. Clinical and experimental observations argue for a hemispheric asymmetry in the processing of appetitive and aversive stimuli. Mesolimbic dopaminergic neurons are part of integrative networks which appear specifically organized in the right and left hemispheres. Dopaminergic neurons may thus be involved in affective processes but in a different manner in the two hemispheres. We tested this hypothesis in the nucleus accumbens of male rats using in vivo voltammetry and a conditioned aversion paradigm to an olfactory stimulus. We found that dopaminergic responses were similar in the two hemispheres following the initial encounter with the stimulus. After conditioning, however, dopaminergic responses to a naturally attractive olfactory stimulus were more elevated in the right nucleus accumbens and responses to an aversive stimulus more marked in the left nucleus. In addition, dopaminergic responses displayed an intraaccumbal regionalization, in particular opposite variations were obtained in the core and shell subterritories in response to the aversive situation. These results may provide new insights in the understanding of the relative contribution of the two hemispheres in affective perception in normal and psychopathological conditions.
1. Eight new proteins have been identified and purified from the nasal tissue of the old-world porcupine. 2. All of them show good binding activity to tritiated 2-isobutyl-3-methoxypyrazine. 3. They show values of molecular mass, in denaturing conditions, between 18 and 23 kDa, and of isoelectric points between 4.2 and 4.6. 4. This represents the first example of more than two odorant-binding proteins (OBPs) found in the same animal species and could support a discriminating function of these proteins in the process of odour perception.
Genetic variation in oral sensation presumably influences ingestive behaviors through sensations arising from foods and beverages. Here, we investigated the influence of taste phenotype [6-n-propylthiouracil (PROP) bitterness, fungiform papillae (FP) density] on sweet and creamy sensations from sugar/fat mixtures. Seventy-nine subjects (43 males) reported the sweetness and creaminess of water or milk (skim, whole, heavy cream) varying in sucrose (0-20% w/v) on the general Labeled Magnitude Scale. Sweetness grew with sucrose concentration and when shifting from water to milk mixtures--the growth was greatest for those tasting PROP as most bitter. At higher sucrose levels, increasing fat blunted the PROP-sweet relationship, whereas at lower levels, the relationship was effectively eliminated. Perceived sweetness of the mixture exceeded that predicted from the sum of components at low sucrose concentrations (especially for those tasting PROP most bitter) but fell below predicted at high concentrations, irrespective of fat level. Creaminess increased greatly with fat level and somewhat with sucrose. Those tasting PROP most bitter perceived greater creaminess in the heavy cream across all sucrose levels. Perceived creaminess was somewhat lower than predicted, irrespective of PROP bitterness. The FP density generally showed similar effects as PROP on sweetness and creaminess, (but to a lesser degree) and revealed potential taste-somatosensory interactions in weakly sweet stimuli. These data support that taste phenotype affects the nature of enhancement or suppression of sweetness and creaminess in liquid fat/sugar mixtures. Taste phenotype effects on sweetness and creaminess likely involve differential taste, retronasal olfactory, and somatosensory contributions to these perceptual experiences.
Chronic experiments were carried out with 19 adult cats. It is demonstrated that following a premesencephalic sectioning of the brain stem, with the lemniscal pathways being spared, on the second and third day after the surgery, auditory, olfactory and skin stimulations caused diffusive activation of the neocortex. Photic stimulation, though evoking responses in the visual cortex, was unable to desynchronize the neocortical electrical activity. Taking into account the data on the organization of hypothalamic afferent connections, it is suggested that diffuse activation of the neocortex in cats, when the mesencephalic reticular formation is completely excluded, occurs during auditory, olfactory and skin stimulations due to excitation of the posterior hypothalamus.
Experiments were performed in goldfish to determine the effects of a short-term exposure (24 h) to atrazine or diuron (0.5, 5, 50 microgram/L) on some behavior endpoints related to swimming and social activities. Observations were also made to assess the influence of such exposure on the behavioral responses of fish to the flow of a crude skin extract solution from conspecifics, active in social chemocommunication and producing alarm behaviors. Additive tests were run to check the behavioral responses of previously unexposed goldfish to the flow of a solution of atrazine- or diuron-contaminated water, at three concentrations (0.1, 1, 10 mg/L). Significant burst swimming reactions appeared in response to a 24-h exposure to atrazine, at the lowest concentration tested (0.5 microgram/L). A 24-h exposure to 5 microgram/L atrazine or diuron was found to induce various significant behavioral alterations in fish. At this concentration, both herbicides decreased grouping behavior and atrazine also increased surfacing activity. Herbicide-exposed fish showed a decreased grouping behavior during the flow of the skin extract solution. Sheltering was also decreased during the flow of the biological solution in fish exposed to atrazine. Moreover, fish exposed to diuron clearly displayed attraction responses to the flow of the skin solution. Previously unexposed fish showed a significant increase in burst swimming reactions in response to the flow of a solution of atrazine- or diuron-contaminated water, at all concentrations tested (0.1, 1, 10 mg/L). Furthermore, the diuron-contaminated flow was found to be significantly attractive at the highest concentration. These results indicate that a short-term exposure to a relatively low concentration (5 microgram/L) of atrazine or diuron can affect various behaviors of fish not only directly but also indirectly by altering the chemical perception of natural substances of eco-ethological importance. In consideration of the basic role of olfaction in fish behavior, these results also emphasize the need for further developments on the possible effects of aquatic toxicants on olfactory-mediated behaviors.
INTRODUCTION: Sense of smell is susceptible to various changes, both in physiological and in numerous pathological conditions. Of quantitative disorders of smell, hyposmia and anosmia are quite common, whereas of qualitative disorders parosmia is most frequent. The aim of this paper was to examine impact of bilateral nasal polyposis on olfactory function. MATERIAL AND METHODS: The research was carried out at the Nose, Ear and Throat Clinic in Novi Sad. It included 80 examinees, 40 (20 male, 20 female) with bilateral nasal polyposis, while 40 examinees belonged to the control group (20 male, 20 female) without symptoms of nasal polyposes. Fortunato-Niccolini olfactometer was used for this examination. RESULTS AND DISCUSSION: In patients with bilateral nasal polyposis the average perception threshold values for examined odors were 15.50 ccm of odorous air, while in the control group they were 10.20 ccm of odorous air. The average identification threshold values for examined odors in patients with bilateral nasal polyposis were 18.80 ccm of odorous air, while in the control group they were 13.55 ccm of scented air. T-test showed that values of both thresholds were statistically significantly higher (p<0.01) in patients with bilateral nasal polyposis in relation to the control group. CONCLUSION: Olfactory deficit in patients with bilateral nasal polyposis is explained by difficult or impossible passage of odors into the olfactory region.
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Using a limited set of odorants, previous studies have indicated that the ability of humans to discriminate and identify the components of olfactory mixtures is limited to approximately four. However, the ability to generalize these results may have been limited by specific neural or cognitive interactions among the particular odorants used. In the present experiment, 41 subjects examined the influence of odor type (different individual odorants), from two very different odor sets, on the perception of the components of complex mixtures. One set contained odors that were selected by an expert panel to blend well in mixtures (good blenders), whereas the other contained odors that blended poorly in mixtures (poor blenders). The stimuli were common, dissimilar odorants of equivalent, moderate intensity, each of which was a single chemical. A computer-controlled air dilution olfactometer delivered a single odorant or a mixture containing up to eight odorants. Although the poor blenders were more easily discriminated, this superiority was displayed within a narrow range, and the ability of subjects to identify mixture components with either odor set was limited to approximately four. The results indicate that, whereas odor type can alter which odorants will be perceived in a mixture, the limited capacity to discriminate mixture components is independent of the type of odorants. These findings are discussed in terms of their implications for olfactory coding.
We have monitored the patterns of activation of five muscles during flight initiation of Drosophila melanogaster: the tergotrochanteral muscle (a mesothoracic leg extensor), dorsal longitudinal muscles #3, #4 and #6 (wing depressors), and dorsal ventral muscle #Ic (a wing elevator). Stimulation of a pair of large descending interneurons, the giant fibers, activates these muscles in a stereotypic pattern and is thought to evoke escape flight initiation. To investigate the role of the giant fibers in coordinating flight initiation, we have compared the patterns of muscle activation evoked by giant fiber stimulation with those during flight initiations executed voluntarily and evoked by visual and olfactory stimuli. Visually elicited flight initiations exhibit patterns of muscle activation indistinguishable from those evoked by giant fiber stimulation. Olfactory-induced flight initiations exhibit patterns of muscle activation similar to those during voluntary flight initiations. Yet only some benzaldehyde-induced and voluntary flight initiations exhibit patterns of muscle activation similar to those evoked by giant fiber stimulation. These results indicate that visually elicited flight initiations are coordinated by the giant fiber circuit. By contrast, the giant fiber circuit alone cannot account for the patterns of muscle activation observed during the majority of olfactory-induced and voluntary flight initiations.
A psychophysical detection test was used to measure the response of human subjects to 'good' and 'bad' smells. Different intensities and frequencies of odour stimulation were delivered by an olfactometer and the responses to a group of malodours (valeric acid, skatol, butyric acid) and pleasant smells (amyl acetate, cis-3-hexenol, linalool) were compared. A mathematical model, a power equation, was used to fit the three-dimensional data plots (dose vs. stimulus frequency vs. response). The model was able to distinguish between malodours and pleasant odours on the basis of the values of parameters describing dose-response and adaptation/habituation. We show that the olfactory system adapts/habituates more rapidly to malodours than to pleasant smells, but is much more sensitive to changes in stimulation by malodours than pleasant odours. The degree of adaptation is inversely proportional to stimulus strength. The response profile for women was different to that of men for certain odours, in particular valeric acid, skatol and cis-3-hexenol. The difference lay in their sensitivity and the slope and range of the dose response. Thus, we have shown for the first time that the olfactory system adapts more readily to 'bad' smells than 'good' smells, and that it has a broader range of adaptation for bad smells. As a consequence, the olfactory system is specially responsive to changes in potential olfactory warning signals.
ENT and olfactometric examinations were carried out on 73 workers at an electrochemical plant involved in the production of cadmium-nickel batteries, where cadmium fumes were emitted into the workplace. Exposure levels exceeded the maximum allowable concentrations by about 1-2 times. The controls included 43 non-exposed, age- and cigarette-smoking-matched people. The olfactometric tests were carried out by the blast injection method, using natural coffee, aniseed, lemon and mint oils; two threshold measurements were assessed: maximum perceptible odour (MPO) and minimum identifiable odour (MIO). In addition, blood chemistries and urinalysis were carried out. The study revealed the smell lesion in 45.2% of the exposed group vs 4.6% of the controls. A statistically significant correlation between olfactory dysfunction and cadmium concentrations in the blood and urine was found; however, no correlation with the duration of employment was observed. It seems most likely that cigarette smoking, which is a considerable source of cadmium, may intensify this dysfunction, hence heavy smokers should not work in conditions of cadmium exposure.
Odor and irritation sensitivity for methyl isobutyl ketone (MIBK) was evaluated by obtaining olfactory detection thresholds and irritation (lateralization) thresholds, as well as perceived odor intensity and irritation ratings for three predetermined concentrations of MIBK, acetone, and phenylethyl alcohol. Subsequently, perceived annoyance ratings for the three concentrations were measured for 25 of the 40 volunteers. The mean odor detection threshold for MIBK was 10 ppm, and mean lateralization threshold was 8874 ppm. Calculating the fifth percentile for lateralization thresholds revealed that 95% of the sample population did not experience sensory irritation at or below 1802 ppm. Thus, while odor thresholds were well below the current recommended exposure limits (50 ppm, threshold limit value; 75 ppm short-term exposure limit, American Conference of Governmental Industrial Hygienists), irritation thresholds were significantly higher. Odor and irritation intensity ratings for the chemicals increased with increasing concentrations and were higher for MIBK than for acetone. However, when the affective component of the irritation response (annoyance) was rated separately from the sensory component (perceived irritation), no significant differences were found between the irritancy of MIBK and acetone, suggesting that negative hedonic evaluations of MIBK (perhaps based on odor unfamiliarity) contributed to ratings of perceived irritation. These results validate coupling affective and sensory ratings to more effectively examine the human response to volatile stimuli. Results indicate that intranasal sensory irritation from MIBK will not be experienced at or near current exposure levels. Notably, the best predictors of perceived irritation to high concentrations of MIBK were those measures related to its odor, not to the threshold for sensory irritation, suggesting that negative responses to MIBK involve reactions to olfactory properties.
Whether pigeons use visual landmarks for orientation from familiar locations has been a subject of debate. By recording the directional choices of both anosmic and control pigeons while exiting from a circular arena we were able to assess the relevance of olfactory and visual cues for orientation from familiar sites. When the birds could see the surroundings, both anosmic and control pigeons were homeward oriented. When the view of the landscape was prevented by screens that surrounded the arena, the control pigeons exited from the arena approximately in the home direction, while the anosmic pigeons' distribution was not different from random. Our data suggest that olfactory and visual cues play a critical, but interchangeable, role for orientation at familiar sites.
GAL4-driven targeted expression of tetanus toxin light chain (UAS-TeTxLC) in a subset of chemosensory neurons of the larval antennomaxillary complex (AMC) and pharynx causes abnormal chemosensory behavior in Drosophila melanogaster. Consistent with strongest staining in the dorsal organ (DO), the presumed olfactory organ of the AMC, tetanus toxin-expressing larvae subjected to an olfactory preference assay show anosmic behavior to most volatile substances tested. Furthermore, we observed reduced responses to sodium chloride, fructose, and sucrose in gustatory plate assays. Surprisingly, the entire subset of labeled sensory neurons from the terminal (maxillary) organ (TO) of the AMC was found to project via the antennal nerve to the larval antennal lobe region. The maxillary nerve remained completely unstained. Hence, a subset of neurons from the TO builds an anatomical entity with projections from the DO. Our results suggest that the AMC contains both olfactory and gustatory sensilla, and that the DO is the main olfactory organ in larvae.
In newborn rabbits, small and apparently arbitrary regions of the olfactory bulb and associated epithelium appear capable of a high degree of odor processing. After medial or lateral removal of up to 80% of the olfactory bulbs, including the accessory bulb, newborn pups were still able to respond appropriately to the pheromone-governing suckling behavior (Expt. I), could rapidly learn to associate a novel, artificial odor with suckling (Expt. II), and continued to respond appropriately to artificial odors learned prior to lesioning (Expt. III). These findings suggest that the perception and recognition of such suckling signals does not depend on the integration of information from the entire bulb or epithelium, and question the extent to which patterns of 2-deoxyglucose uptake in the bulb reflect the neural coding for specific odors. However, as the tasks set here only required detection of odor signals and not true odor discrimination, it may still be that the full bulbar pattern of activation is necessary for higher-order processing, such as distinguishing between odors and attributing different meanings to them.