Neuronal cell types and taste quality coding

Over the past 25 years, there have been two opposing views of how taste information is represented in the activity of gustatory neurons. One view, the across-fiber pattern (AFP) theory, postulates that taste quality is represented by the pattern of activity across the afferent population. Stimuli with similar tastes produce similar patterns of activity. The other view is that activity in a few distinct neuron types codes taste quality in a "labeled-line" fashion. Neurons responding best to sucrose, for example, would represent "sweetness," and those responding best to NaCl would code "saltiness." Some of these neuron types appear to have a biological significance, such as the NaCl-best cells, which receive input about sodium stimuli exclusively from an amiloride-sensitive epithelial ion channel. However, the relatively broad tuning of these neurons makes it unlikely that they are capable of unambiguously coding information about taste quality. Rather, these neuron types play a critical role in establishing unique AFPs that distinguish among taste stimuli. The relative activity across these cell types represent taste quality, much like the patterns of activity across broadly tuned photoreceptors code information about stimulus wavelength.     

Gustatory responses of cortical neurons in rats. II. Information processing of taste quality

The present report was designed to investigate neural coding of taste information in the cerebral cortical taste area of rats. The magnitude and/or type (excitatory, inhibitory, or no-response) of responses of 111 cortical neurons evoked by single concentrations of the four basic taste stimuli (sucrose, NaCl, HCl, and quinine HCl) were subjected to four types of analyses in the context of the four proposed hypotheses of taste-quality coding: across-neuron response-pattern, labeled-line, matrix-pattern, and across-region response-pattern notions (88 histologically located neurons). An across-neuron response-pattern notion assumes that taste quality is coded by differential magnitudes of response across many neurons. This theory utilizes across-neuron correlation coefficients as a metric for the evaluation of taste quality coding. Across-neuron correlations between magnitudes of responses to any pairs of the four basic taste stimuli across 111 cortical neurons were very high and were similar. However, calculations made with net responses (spontaneous rate subtracted) resulted in less positive correlations but still similar values among the various pairs of taste stimuli. This finding suggests that across-neuron response patterns of cortical neurons become less discriminating among taste qualities compared with those of the lower-order neurons. A labeled-line notion assumes that there are identifiable groups of neurons and that taste quality is coded by activity in these particular sets of neurons. Some investigators have classified taste-responsive neurons into best-stimulus categories, depending on their best sensitivity to any one of the four basic stimuli, such as sucrose-best, NaCl-best, HCl-best, and quinine-best neurons; they have suggested that taste can be classified along four qualitative dimensions that correspond to these four neuron types (i.e., four labeled lines). The present study shows that responsiveness of each of the four best-stimulus neurons had similar profiles between peripheral and cortical levels. That is, when the stimuli were arranged along the abscissa in the order of sucrose, NaCl, HCl, and quinine, there is a peak response in one place, and the responses decreased gradually from the peak. However, such response characteristics do not favor the labeled-line theory, since they can be explained in the context of the across-neuron pattern theory. A matrix-pattern notion assumes that taste quality is coded by a spatially arranged matrix pattern of activated neurons.(ABSTRACT TRUNCATED AT 400 WORDS)     

The synaptic connectivity that underlies the noxious transmission and modulation within the superficial dorsal horn of the spinal cord

Noxious stimuli can usually cause the aversive sensations, pain and itch. The initial integration of such noxious information occurs in the superficial dorsal horn of the spinal cord (SDH), which is very important for understanding pain sensation and developing effective analgesic strategies. The circuits formed by pools of neurons and terminals within SDH are accepted as the platform for such complicated integrations and are highly plastic under conditions of inflammatory or neuropathic pain. Recent literature offers a complicated, yet versatile view of SDH intrinsic circuits with both inhibitory and excitatory components. However, our knowledge about the adaptative regulation of SDH local circuits is still far from sufficient due to the incomplete understanding of their organization as they are intermingled with primary afferent fibers (PAFs), poorly understood or identified SDH neurons, somehow contradictory data for descending control systems. A more positive view emphasizes abundant modern data on SDH neuron morphology and physiology riding on the back of significant technological advancements used in neuroscience. Reviewing the current literature on this topic thus produced an integrated understanding of SDH neurons and the SDH local circuits involved in noxious transmission and modulation.     

Temperature modulates taste responsiveness and stimulates gustatory neurons in the rat geniculate ganglion

In humans, temperature influences taste intensity and quality perception, and thermal stimulation itself may elicit taste sensations. However, peripheral coding mechanisms of taste have generally been examined independently of the influence of temperature. In anesthetized rats, we characterized the single-cell responses of geniculate ganglion neurons to 0.5 M sucrose, 0.1 M NaCl, 0.01 M citric acid, and 0.02 M quinine hydrochloride at a steady, baseline temperature (adapted) of 10, 25, and 40 degrees C; gradual cooling and warming (1 degrees C/s change in water temperature >5 s) from an adapted tongue temperature of 25 degrees C; gradual cooling from an adapted temperature of 40 degrees C; and gradual warming from an adapted temperature of 10 degrees C. Hierarchical cluster analysis of the taste responses at 25 degrees C divided 50 neurons into two major categories of narrowly tuned (Sucrose-specialists, NaCl-specialists) and broadly tuned (NaCl-generalists(I), NaCl- generalists(II), Acid-generalists, and QHCl-generalists) groups. NaCl specialists were excited by cooling from 25 to 10 degrees C and inhibited by warming from 10 to 25 degrees C. Acid-generalists were excited by cooling from 40 to 25 degrees C but not from 25 to 10 degrees C. In general, the taste responses of broadly tuned neurons decreased systematically to all stimuli with decreasing adapted temperatures. The response selectivity of Sucrose-specialists for sucrose and NaCl-specialists for NaCl was unaffected by adapted temperature. However, Sucrose-specialists were unresponsive to sucrose at 10 degrees C, whereas NaCl-specialists responded equally to NaCl at all adapted temperatures. In conclusion, we have shown that temperature modulates taste responsiveness and is itself a stimulus for activation in specific types of peripheral gustatory neurons.     

Unilateral nasal obstruction alters sweet taste preference and sweet taste receptors in rat circumvallate papillae

Nasal obstruction causes mouth breathing, and affects the growth and development of craniofacial structures, muscle function in the stomatognathic system, and the taste perceptive system. However, the detailed mechanism underlying the effects of nasal obstruction on taste perception has not been fully elucidated. In this study, we investigated this mechanism using the two-bottle taste preference test, immunohistological analysis, and quantification of the mRNA expression of taste-related molecules in the circumvallate papillae. Neonatal male Wistar rats were divided randomly into control and experimental groups. Rats in the experimental group underwent unilateral nasal obstruction by cauterization of the external nostril at the age of 8 days. Arterial oxygen saturation (SpO₂) was recorded in awake rats using collar clip sensors. Taste preference for five basic taste solutions was evaluated. Immunohistochemical analysis and quantitative real-time polymerase chain reaction (RT-PCR) were conducted to evaluate the expressions of taste-related molecules in the taste cells of the circumvallate papillae. Body weights were similar between the two groups throughout the experimental period. The SpO₂ in the 7- to 12-week-old rats in the experimental group was significantly lower than that in the age-matched rats in the control group. In the two-bottle taste preference test, the sensitivities to sweet taste decreased in the experimental group. The mRNA expression of T1R2, T1R3, α-gustducin, and PLCβ2 was significantly lower in the experimental group than in the control group as determined by quantitative RT-PCR, and the immunohistochemical staining for α-gustducin and PLCβ2 was less prominent. These findings suggest that nasal obstruction may affect sweet taste perception via the reduced expression of taste-related molecules in the taste cells in rat circumvallate papillae.     

Individual mouse taste cells respond to multiple chemical stimuli

Sensory organs are specialized to detect and decode stimuli in terms of intensity and quality. In the gustatory system, the process of identifying and distinguishing taste qualities (e.g. bitter versus sweet) begins in taste buds. A central question in gustatory research is how information about taste quality is extracted by taste receptor cells. For instance, whether and how individual taste cells respond to multiple chemical stimuli is still a matter for debate. A recent study showed that taste cells expressing bitter-responsive taste receptors do not also express sweet-responsive taste receptors and vice versa. These results suggest that the gustatory system may use separate cellular pathways to process bitter and sweet signals independently. Results from electrophysiological studies, however, reveal that individual taste receptor cells respond to stimuli representing multiple taste qualities. Here we used non-invasive Ca²⁺ imaging in slices of lingual tissue containing taste buds to address the issue of quality detection in murine taste receptor cells. We recorded calcium transients elicited by chemical stimuli representing different taste qualities (sweet, salty, sour and bitter). Many receptor cells (38 %) responded to multiple taste qualities, with some taste cells responding to both appetitive ('sweet') and aversive ('bitter') stimuli. Thus, there appears to be no strict and separate detection of taste qualities by distinct subpopulations of taste cells in peripheral gustatory sensory organs in mice.     

The functional role of the T1R family of receptors in sweet taste and feeding

The discovery of the T1R family of Class C G protein-coupled receptors in the peripheral gustatory system a decade ago has been a tremendous advance for taste research, and its conceptual reach has extended to other organ systems. There are three proteins in the family, T1R1, T1R2, and T1R3, encoded by their respective genes, Tas1r1, Tas1r2, and Tas1r3. T1R2 combines with T1R3 to form a heterodimer that binds with sugars and other sweeteners. T1R3 also combines with T1R1 to form a heterodimer that binds with l-amino acids. These proteins are expressed not only in taste bud cells, but one or more of these T1Rs have also been identified in the nasal epithelium, gut, pancreas, liver, kidney, testes and brain in various mammalian species. Here we review current perspectives regarding the functional role of these receptors, concentrating on sweet taste and feeding. We also discuss behavioral findings suggesting that a glucose polymer mixture, Polycose, which rodents avidly prefer, appears to activate a receptor that does not depend on the combined expression of T1R2 and T1R3. In addition, although the T1Rs have been implicated as playing a role in glucose sensing, T1R2 knock-out (KO) and T1R3 KO mice display normal chow and fluid intake as well as normal body weight compared with same-sex littermate wild type (WT) controls. Moreover, regardless of whether they are fasted or not, these KO mice do not differ from their WT counterparts in their Polycose intake across a broad range of concentrations in 30-minute intake tests. The functional implications of these results and those in the literature are considered.     

Bitter-responsive brainstem neurons: Characteristics and functions

The sensation that humans describe as “bitter” is evoked by a large group of chemically diverse ligands. Bitter stimuli are avoided by a range of species and elicit reflex rejection, behaviors considered adaptations to the toxicity of many of these compounds. We review novel evidence for neurons that are narrowly tuned to bitter ligands at the initial stages of central processing. These “B-best” neurons in the nucleus of the solitary tract (NST) and parabrachial nucleus (PBN) respond to multiple types of bitter stimuli and exhibit average responses to bitter tastants that are 6-8 times larger than to moderate concentrations of compounds representing other qualities. However, in the PBN B-best units are appreciably activated by intense salt and acid. Neurons broadly sensitive to salts and acids (“AN” neurons) also responded to bitter stimuli. This sensitivity appeared restricted to stronger intensities of ionic bitters, as cycloheximide remained ineffective across concentrations. In addition to chemosensitive profile, B-best neurons were also distinctive with regard to their posterior receptive fields, long latencies, slow firing rates and projection status. Compared to B-best NST cells, those in the PBN received increased convergence from anterior and posterior receptive fields and responded to a greater number of bitter stimuli. We conclude that B-best neurons likely contribute to pathways underlying gaping, aversive hedonic quality and taste coding. The differential responsiveness of B-best and AN neurons to ionic and nonionic bitter ligands also suggests a potential substrate for discrimination within this quality.     

Afferent connections of the parabrachial nucleus in C57BL/6J mice

Although the mouse is an experimental model with an increasing importance in various fields of neuroscience, the characteristics of its central gustatory pathways have not yet been well documented. Recent electrophysiological studies using the rat and hamster have revealed that taste processing in the brainstem gustatory relays is under the strong influence of inputs from forebrain gustatory structures. In the present study, we investigated the organization of afferent projections to the mouse parabrachial nucleus (PbN), which is located at a key site between the brainstem and gustatory, viscerosensory and autonomic centers in the forebrain. We made injections of the retrograde tracer fluorogold centered around the “waist” area of the PbN, whose neurons are known to be highly responsive to taste stimuli. Retrogradely labeled neurons were found in the infralimbic, dysgranular and agranular insular cortex as well as the claustrum; the bed nucleus of the stria terminalis and the substantia innominata; the central nucleus of the amygdala; the lateral and medial preoptic areas, the paraventricular, the dorsomedial, the ventromedial, the arcuate, and the lateral hypothalamic areas; the periaqueductal gray, the substantia nigra pars compacta, and the ventral tegmental area; the supratrigeminal nucleus, rostral and caudal nucleus of the solitary tract; the parvicellular intermediate and gigantocellular reticular nucleus; the caudal and interpolar divisions of the spinal trigeminal nucleus, dorsomedial spinal trigeminal nucleus, and the area postrema. Numbers of labeled neurons in the main components of the gustatory system including the insular cortex, bed nucleus of the stria terminalis, central nucleus of the amygdala, lateral hypothalamus, and rostral nucleus of the solitary tract were quantified. These results are basically consistent with those of the previous rat and hamster studies, but some species differences were found. Functional implications of these afferent inputs are discussed with an emphasis on their role in taste.     

Neutrophil responses to injury or inflammation impair peripheral gustatory function

The adult peripheral taste system is capable of extensive functional plasticity after injury. Sectioning the chorda tympani (CT), a primary sensory afferent nerve, elicits transient changes in the uninjured, contralateral population of taste receptor cells. Remarkably, the deficits are specific to the sodium transduction pathway. Normal function is quickly restored in the intact nerve, in parallel with an influx of macrophages to both the denervated and uninjured sides of the tongue. However, changing the dietary environment by restricting sodium blocks the macrophage response and prolongs functional alterations. Since the functional deficits occur before macrophages are present in the peripheral taste system, we hypothesized that neutrophils play a role in modulating neural responses in the intact CT. First, the dynamics of the neutrophil response to nerve injury were analyzed in control-fed and sodium-deficient rats. Nerve sectioning briefly increased the number of neutrophils on both the denervated and uninjured sides of the tongue. The low-sodium diet amplified and extended the bilateral neutrophil response to injury, in parallel with the persistent changes in sodium taste function. To test the impact of neutrophils on taste function, we depleted these cells prior to nerve sectioning and recorded neural responses from the intact CT. This treatment restored normal sodium responses in the uninjured nerve. Moreover, recruiting neutrophils to the tongue induced deficits in sodium taste function in both CT nerves. Neutrophils play a critical role in ongoing inflammatory responses in the oral cavity, and may induce changes in taste perception. We also suggest that balanced neutrophil and macrophage responses enable normal neural responses after neural injury.     

Behavioral Analysis of Drosophila Transformants Expressing Human Taste Receptor Genes in the Gustatory Receptor Neurons

Abstract: Transgenic Drosophila expressing human T2R4 and T2R38 bitter-taste receptors or PKD2L1 sour-taste receptor in the fly gustatory receptor neurons and other tissues were prepared using conventional Gal4/UAS binary system. Molecular analysis showed that the transgene mRNAs are expressed according to the tissue specificity of the Gal4 drivers. Transformants expressing the transgene taste receptors in the fly taste neurons were then studied by a behavioral assay to analyze whether transgene chemoreceptors are functional and coupled to the cell response. Since wild-type flies show strong aversion against the T2R ligands as in mammals, the authors analyzed the transformants where the transgenes are expressed in the fly sugar receptor neurons so that they promote feeding ligand-dependently if they are functional and activate the neurons. Although the feeding preference varied considerably among different strains and individuals, statistical analysis using large numbers of transformants indicated that transformants expressing T2R4 showed a small but significant increase in the preference for denatonium and quinine, the T2R4 ligands, as compared to the control flies, whereas transformants expressing T2R38 did not. Similarly, transformants expressing T2R38 and PKD2L1 also showed a similar preference increase for T2R38-specific ligand phenylthiocarbamide (PTC) and a sour-taste ligand, citric acid, respectively. Taken together, the transformants expressing mammalian taste receptors showed a small but significant increase in the feeding preference that is taste receptor and also ligand dependent. Although future improvements are required to attain performance comparable to the endogenous robust response, Drosophila taste neurons may serve as a potential in vivo heterologous expression system for analyzing chemoreceptor function.     

Precise temporal responses in whisker trigeminal neurons

The ability of rats using their whiskers to perform fine tactile discrimination rivals that of humans using their fingertips. Rats must perform these discriminations rapidly and accurately while palpating the environment with their whiskers. This suggests that whisker-derived inputs produce a robust and reliable code, capable of capturing complex, high-frequency information. The first neural representation of whisker-derived stimulus information is in primary afferent neurons of the trigeminal ganglion. Here we demonstrate that there is a continuum of direction-dependent response profiles in trigeminal neurons and provide the first quantitative analysis of the encoding of complex stimuli by these neurons. We show that all classes of trigeminal ganglion neurons respond with highly reproducible temporal spike patterns to transient stimuli. Such a robust coding mechanism may allow rapid perception of complex tactile features.     

Sparse and dense coding of natural stimuli by distinct midbrain neuron subpopulations in weakly electric fish

While peripheral sensory neurons respond to natural stimuli with a broad range of spatiotemporal frequencies, central neurons instead respond sparsely to specific features in general. The nonlinear transformations leading to this emergent selectivity are not well understood. Here we characterized how the neural representation of stimuli changes across successive brain areas, using the electrosensory system of weakly electric fish as a model system. We found that midbrain torus semicircularis (TS) neurons were on average more selective in their responses than hindbrain electrosensory lateral line lobe (ELL) neurons. Further analysis revealed two categories of TS neurons: dense coding TS neurons that were ELL-like and sparse coding TS neurons that displayed selective responses. These neurons in general responded to preferred stimuli with few spikes and were mostly silent for other stimuli. We further investigated whether information about stimulus attributes was contained in the activities of ELL and TS neurons. To do so, we used a spike train metric to quantify how well stimuli could be discriminated based on spiking responses. We found that sparse coding TS neurons performed poorly even when their activities were combined compared with ELL and dense coding TS neurons. In contrast, combining the activities of as few as 12 dense coding TS neurons could lead to optimal discrimination. On the other hand, sparse coding TS neurons were better detectors of whether their preferred stimulus occurred compared with either dense coding TS or ELL neurons. Our results therefore suggest that the TS implements parallel detection and estimation of sensory input.     

Neuron types, receptors, behavior, and taste quality

Neurophysiological studies on chorda tympani (CT) single fibers and behavioral studies on generalization of learned aversions in hamsters (Mesocricetus auratus) are reviewed. The work on hamsters is compared to work on other species, including the laboratory rat and several primate species, including humans. This body of data demonstrates associations between response profiles of physiologically defined specialist CT neurons and behavioral stimulus generalizations on one hand, and characteristics of putative taste receptors, on the other. Response profiles of generalist CT neurons are similarly associated with receptor characteristics, but are not associated with specific behavioral discriminations. The associations of peripheral nerve data with both receptor and behavior strongly suggest specific codes for "sucrose-like" and "NaCl-like" taste qualities. Definitive conclusions regarding "patterns" or "labeled lines" requires an understanding of mechanisms of central neural processing of the several specialist and generalist taste-afferent inputs.     

Chronic restraint stress in rats suppresses sweet and umami taste responses and lingual expression of T1R3 mRNA

Effects of chronic restraint stress on the taste responses to five basic taste qualities were investigated electrophysiologically in the rat chorda tympani. In addition, the mRNA expression for T1R3, the common G-protein-coupled receptor (GPCR) for sweet and umami tastes, was studied quantitatively by RT-PCR after such stress. Rats were restrained in a small cylindrical restrainer made of steel wire for 8h daily for 14 successive days. The integrated responses to sweet and umami tastes, as recorded from the chorda tympani, were significantly suppressed after such stress, but the other three basic taste responses were unaffected. Expression of T1R3 mRNA in the fungiform papillae, as estimated by RT-PCR, was slightly reduced by the stress, and a quantitative real time RT-PCR study revealed a significant suppression of T1R3 mRNA expression in the stress group. These results suggest that the observed stress-induced changes in taste sensation could be caused by a peripheral disorder of the transduction mechanism in taste-receptor cells, involving in particular a stress-induced inhibition of T1R3 expression.     

Convergence of sensory systems in the orbitofrontal cortex in primates and brain design for emotion

In primates, stimuli to sensory systems influence motivational and emotional behavior via neural relays to the orbitofrontal cortex. This article reviews studies on the effects of stimuli from multiple sensory modalities on the brain of humans and some other higher primates. The primate orbitofrontal cortex contains the secondary taste cortex, in which the reward value of taste is represented. It also contains the secondary and tertiary olfactory cortical areas, in which information about the identity and also about the reward value of odors is represented. A somatosensory input is revealed by neurons that respond to the viscosity of food in the mouth, to the texture (mouth feel) of fat in the mouth, and to the temperature of liquids placed into the mouth. The orbitofrontal cortex also receives information about the sight of objects from the temporal lobe cortical visual areas. Information about each of these modalities is represented separately by different neurons, but in addition, other neurons show convergence between different types of sensory input. This convergence occurs by associative learning between the visual or olfactory input and the taste. In that emotions can be defined as states elicited by reinforcers, the neurons that respond to primary reinforcers (such as taste and touch), as well as learn associations to visual and olfactory stimuli that become secondary reinforcers, provide a basis for understanding the functions of the orbitofrontal cortex in emotion. In complementary neuroimaging studies in humans, it is being found that areas of the orbitofrontal cortex are activated by pleasant touch, by painful touch, by taste, by smell, and by more abstract reinforcers such as winning or losing money. Damage to the orbitofrontal cortex in humans can impair the learning and reversal of stimulus-reinforcement associations and thus the correction of behavioral responses when these are no longer appropriate because previous reinforcement contingencies change. It is striking that humans and other catarrhines, being visual specialists like other anthropoids, interface the visual system to other sensory systems (e.g., taste and smell) in the orbitofrontal cortex.     

Gustatory responses of cortical neurons in rats. III. Neural and behavioral measures compared

The responses of 39 cortical neurons to 13 kinds of taste stimuli including the four putative basic taste solutions (sucrose, NaCl, HCl, and quinine HCl) applied to the anterior portion of the tongue were recorded extracellularly in lightly anesthetized rats. The neural responses were analyzed in terms of the four hypotheses of quality coding: across-neuron response pattern, labeled-line, matrix pattern, and across-region response pattern notions. Animals were given a conditioned taste aversion to one of the 11 stimuli by pairing it with a gastrointestinal illness caused by intraperitoneal injection of 0.15 M LiCl. Behavioral taste profiles were constructed for each stimulus from the suppression of rate of drinking, which indicates the extent of generalization of aversion to each of the four basic taste stimuli. Neural taste profiles of each taste stimulus, which indicate the relation of the taste of a stimulus to each taste of the four basic stimuli, differed more or less depending on the kind of quality-coding notions employed. Among the four analyses, across-region correlation coefficients that were derived from an across-region response-pattern theory showed the highest correlation with the behavioral suppression rates. Therefore we conclude that processing of taste information in the cortex involves differences in both response magnitude across neurons and the spatial localization of those neurons. Fluid intake per day of each of the 12 taste solutions was measured by the single-bottle preference method. When the amount of intake was described in terms of an hedonic index (HI), which indicates the hedonic aspect of the taste of each solution, HI's for sucrose, NaCl, HCl, and quinine were 1.17, 0.43, -0.49, and -0.89, respectively. These values represent the degree of deviation of solution intake above (i.e., preferable) or below (aversive) the standard water intake. Then, HI's were calculated for each of the 12 taste stimuli based on the neural taste profiles and actual HI's for each of the four basic taste stimuli. The correlations between the calculated and the actual (or behaviorally obtained) HI's were very high (ranging from 0.832 to 0.941). This result suggests that the hedonic dimension of taste can be matched well by any one of the four proposed hypotheses.     

A comparison between taste avoidance and conditioned disgust reactions induced by ethanol and lithium chloride in preweanling rats

Adult rats display taste avoidance and disgust reactions when stimulated with gustatory stimuli previously paired with aversive agents such as lithium chloride (LiCl). By the second postnatal week of life, preweanling rats also display specific behaviors in response to a tastant conditioned stimulus (CS) that predicts LiCl‐induced malaise. The present study compared conditioned disgust reactions induced by LiCl or ethanol (EtOH) in preweanling rats. In Experiment 1 we determined doses of ethanol and LiCl that exert similar levels of conditioned taste avoidance. After having equated drug dosage in terms of conditioned taste avoidance, 13‐day‐old rats were given a single pairing of a novel taste (saccharin) and either LiCl or ethanol (2.5 g/kg; Experiment 2). Saccharin intake and emission of disgust reactions were assessed 24 and 48 hr after training. Pups given paired presentations of saccharin and the aversive agents (ethanol or LiCl) consumed less saccharin during the first testing day than controls. These pups also showed more aversive behavioral reactions to the gustatory CS than controls. Specifically, increased amounts of grooming, general activity, head shaking, and wall climbing as well as reduced mouthing were observed in response to the CS. Conditioned aversive reactions but not taste avoidance were still evident on the second testing day. In conclusion, a taste CS paired with postabsorptive effects of EtOH and LiCl elicited a similar pattern of conditioned rejection reactions in preweanling rats. These results suggest that similar mechanisms may be underlying CTAs induced by LiCl and a relatively high EtOH dose. © 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 545–557, 2010.