Estradiol benzoate can function as an unconditioned stimulus in a conditioned taste aversion paradigm

The extent to which gonadal steroid hormones can serve as unconditioned stimuli in a conditioned taste aversion paradigm was examined in Rockland-Swiss albino mice. With saccharin serving as the conditioned stimulus, subcutaneously injected estradiol benzoate, but not progesterone or testosterone propionate, was found to be a potent unconditioned stimulus in both male and female mice. Dose-response effects were also observed; increasing dosages of estradiol benzoate led to increasingly stronger conditioned aversions in both males and females. The aversion detected in males was more resistant to extinction than that seen in females. Prepubertal gonadectomy reversed the sex-dependent effects of estradiol benzoate in learned aversions in adulthood; castration of males promoted the extinction process, whereas ovariectomy of females retarded extinction. The results may be useful for our understanding of the mechanisms involved in conditioned taste aversion learning as well as a wide array of hormone-dependent behavioral responses.     

Hippocampus, ageing, and taste memories

Previous studies have shown that ageing may induce deficits in hippocampal-dependent learning and memory tasks, the spatial task being most extensively applied in rats. It is proposed that taste learning and memory tasks may assist in understanding the ageing of memory systems, giving access to a more complete picture. Taste learning tasks allow us to explore a variety of learning phenomena in safe and aversive memories using similar behavioral procedures. In demanding the same sensory, response, and motivational requirements, this approach provides reliable comparisons between the performance of hippocampal lesioned and aged rats in different types of memory. Present knowledge on the effect of both ageing and hippocampal damage in complex taste learning phenomena is reviewed. Besides inducing deficits in hippocampal-dependent phenomena, such as blocking of conditioned taste aversion, while at the same time leaving intact nonhippocampal-dependent effects, such as latent inhibition, ageing is also associated with an increased neophobia by previous aversive taste memories and enhanced taste aversion conditioning which cannot be explained by age-related changes in taste or visceral distress sensitivity. In all, the results indicate a peculiar organization of the memory systems during aging that cannot be explained by a general cognitive decline or exclusively by the decay of the hippocampal function.     

Parabrachial unit activities after the acquisition of conditioned taste aversion to a non-preferred HCl solution in rats

Abstract In a behavioral experiment, rats reliably acquired a taste aversion to non-preferred 0.01 M HCl that had been previously paired with intraperitoneal injection of 0.15 M LiCl. These rats showed aversions to other acidic solutions such as malic acid and tartaric acid. In a neurophysiological experiment, the neuronal activities of the parabrachial nucleus (PBN) were recorded after the acquisition of conditioned taste aversion (CTA) to 0.01 M HCl in urethane-anesthetized rats. Neuronal responses to the conditioned stimulus (CS) did not change on the whole but decreased in the dorsal region to the brachium conjunctivum. The proportion of HCl-best to NaCl-best units was lower in the CTA group than in controls. The spontaneous firing rate was lower in the CTA group than in controls. Correlation coefficients between the HCl CS and normally preferred tastes (sucrose and NaCl) were more negative and those between HCl and quinine were more positive in the CTA group than in the controls. These results may be explained by the notion that gustatory responses of PBN neurons are concerned with alterations in taste hedonics after the acquisition of conditioned taste aversions.     

Taste aversion learning in preweanling rats exposed to alcohol prenatally

The effects of prenatal alcohol exposure on the development of a conditioned taste aversion were examined in preweanling rat pups. Mothers of these pups were fed isocaloric liquid diets containing either 35 or 0% ethanol-derived calories (EDC) from gestation days 6 through 20. A pair-feeding procedure was employed, and an ad lib lab chow control group was also included. At 5, 10, or 15 days of age, pups were infused with a saccharin solution through a cannula implanted in the oral cavity. Half of the pups in each group were then injected with lithium chloride (LiCl), which served as the poisoning agent, and the other half with sodium chloride (NaCl) as a control. Animals were subsequently tested for a conditioned aversion to the saccharin solution. At 15 days of age, all of the pups in the LiCl-poisoned group demonstrated a conditioned taste aversion to the saccharin solution, but the degree of this aversion was less in alcohol-exposed offspring. At 10 days of age, a taste aversion was learned, although it was not as strong as that shown by 15-day-old pups, and it appeared to be learned equally well by all of the prenatal treatment groups. At 5 days of age, there was marginal support for taste aversion learning. Again, it did not interact with prenatal treatment. The ontogenic differences in taste aversion learning exhibited by alcohol-exposed offspring relative to controls are discussed in terms of altered hippocampal development.     

Estradiol accelerates extinction of lithium chloride-induced conditioned taste aversions through its illness-associated properties

Estradiol accelerates extinction of LiCl-induced conditioned taste aversions when it is present during a period that starts 2-3 days after acquisition and extends throughout extinction (before and during extinction). It has been suggested that estradiol acts before, not during, extinction and that its effect on extinction is associated with its illness-inducing properties. This hypothesis is based on previous work which shows an attenuation of conditioned taste aversion learning when rats are exposed to illness-inducing agents during a period that starts 2 days after acquisition and ends 2 days before extinction trials are initiated. Four experiments were designed to test elements of this hypothesis. The first two experiments demonstrated that if an estradiol-filled Silastic capsule is implanted before extinction of a LiCl-induced aversion, when the conditioned taste is not present, it accelerates extinction, but if it is implanted during extinction, when the conditioned taste is present, it prolongs extinction. The third experiment showed that the same dose of estradiol that accelerates extinction of a LiCl-induced aversion was effective in producing a conditioned taste aversion when it was present for 18 h after consumption of a novel sucrose solution. The fourth experiment indicated that serum levels of estradiol were elevated during the 18 h. These results are consistent with the hypothesis that the acceleration of extinction by estradiol is associated with its illness-inducing properties. It is suggested that estradiol acts on neural areas that mediate illness information and that one of these areas, the area postrema is necessary for estradiol to accelerate extinction of a LiCl-induced aversion.     

Phenylthiocarbamide produces conditioned taste aversions in mice

Previous work has demonstrated that SWR/J (SW) mice avoid phenylthiocarbamide (PTC) to a greater degree than C3HeB/FeJ mice in 48 h, two-bottle preference tests given in ascending series. The authors hypothesized, based also on previous work, that SW mice might form a conditioned taste aversion over time due to the toxic properties of PTC. We directly tested this hypothesis by attempting to condition a taste aversion to sucrose by injections of PTC. In experiment 1, PTC was nearly as effective as a strong dose of LiCl in reducing sucrose drinking. In experiment 2, the sucrose aversions were parametrically modified by both sucrose concentration and PTC dose, a hallmark of conditioned taste aversion. We conclude that PTC can cause a conditioned taste aversion and discuss the importance of considering toxic effects of aversive tastants when analyzing behavioral strain differences.     

The effects of acute corticosterone on lithium chloride-induced conditioned place aversion and locomotor activity in rats

Acute administration of corticosterone (CORT) facilitates learning in a number of associative paradigms including lithium chloride (LiCl)-induced conditioned taste aversion learning. The present study examined the effects of acute CORT on LiCl-induced conditioned place aversions in male rats. Automated open-fields were partitioned into two chambers distinct in tactile and visual cues. Animals received either LiCl (64 mg/kg, 0.15 M) or saline (NaCl, 0.15 M) followed 10 min later by either CORT (5 mg/kg) or beta-cyclodextrin vehicle (45%) prior to placement in one of the chambers. Control rats received NaCl-Vehicle paired with both chambers. Three experimental groups received either NaCl-CORT, LiCl-Vehicle or LiCl-CORT paired with the preferred chamber and NaCl-Vehicle (control) paired with the non-preferred chamber. During extinction trials, animals were allowed to choose between the two chambers. Locomotor activity and its distribution within the chambers were assessed during both conditioning and extinction trials. CORT administration produced significant increases in a variety of measures of locomotor activity during conditioning trials. During extinction trials both LiCl groups displayed a conditioned place aversion while the NaCl-CORT group did not. In addition, significant increases in vertical activity were recorded in both LiCl groups in the LiCl-paired chamber. Moreover, CORT administration had no effect on LiCl-induced conditioned place aversion as time spent in the LiCl-paired chamber did not significantly differ between LiCl-Vehicle and LiCl-CORT groups. Significant increases in a number of measures of horizontal activity were also observed in both CORT groups. The present study shows that acute CORT administration does not significantly influence LiCl-induced conditioned place aversions and suggests that the facilitatory effects of acute CORT administration on learning are highly context-dependent.     

Ontogenetic differences in sensitivity to LiCl- and amphetamine-induced taste avoidance in preweanling rats

When amphetamine is associated with a tastant conditioned stimulus, rats learn to avoid the taste even when employing doses that promote conditioned place preference. One hypothesis raised to account for this effect proposes that taste avoidance induced by amphetamine may be motivated by fear. A sensitive period has been identified in the rat (until postnatal day 10) in which infants learn conditioned appetitive effects to stimuli to which aversions are conditioned after this period. Exogenous administration of corticosterone within this period reverses this effect, generating aversive conditioning. In the present study, we tested conditioning of aversions to amphetamine or LiCl, within and after the sensitive period (Experiments 1 and 2). A third experiment evaluated unconditioned rejection of an aversive quinine solution within the sensitive period. Finally, we tested whether corticosterone administration before conditioning modulates amphetamine-induced taste avoidance. After the sensitive period, infant rats rejected the solution paired with amphetamine or LiCl after 2 conditioning trials, but within the sensitive period, aversions were conditioned only by LiCl and after 4 conditioning trials. Amphetamine-induced taste avoidance was not observed even when corticosterone was administered before conditioning. Additionally, during the sensitive period, a low LiCl dose promoted conditioned taste preference. According to Experiment 3, parameters employed in this study were suitable to yield rejection of aversive solutions within the sensitive period. These results suggest that during the sensitive period, there is a notable resistance to the acquisition of taste avoidance induced by amphetamine. The present experimental framework may represent a useful tool for studying mechanisms underlying taste avoidance and aversion effects.     

Parallel reinforcement pathways for conditioned food aversions in the honeybee

Avoiding toxins in food is as important as obtaining nutrition. Conditioned food aversions have been studied in animals as diverse as nematodes and humans [1, 2], but the neural signaling mechanisms underlying this form of learning have been difficult to pinpoint. Honeybees quickly learn to associate floral cues with food [3], a trait that makes them an excellent model organism for studying the neural mechanisms of learning and memory. Here we show that honeybees not only detect toxins but can also learn to associate odors with both the taste of toxins and the postingestive consequences of consuming them. We found that two distinct monoaminergic pathways mediate learned food aversions in the honeybee. As for other insect species conditioned with salt or electric shock reinforcers [4-7], learned avoidances of odors paired with bad-tasting toxins are mediated by dopamine. Our experiments are the first to identify a second, postingestive pathway for learned olfactory aversions that involves serotonin. This second pathway may represent an ancient mechanism for food aversion learning conserved across animal lineages.     

The taste of monosodium glutamate (MSG), L-aspartic acid, and N-methyl-D-aspartate (NMDA) in rats: are NMDA receptors involved in MSG taste?

Monosodium glutamate (MSG) is believed to elicit a unique taste perception known as umami. We have used conditioned taste aversion assays in rats to compare taste responses elicited by the glutamate receptor agonists MSG, L-aspartic acid (L-Asp), and N-methyl-D-aspartate (NMDA), and to determine if these compounds share a common taste quality. This information could shed new light upon the receptor mechanisms of glutamate taste transduction. Taste aversions to either MSG, L-Asp or NMDA were produced by injecting rats with LiCl after they had ingested one of these stimuli. Subsequently, rats were tested to determine whether they would ingest any of the above compounds. The results clearly show that a conditioned aversion to MSG generalized to L-Asp in a dose-dependent manner. Conversely, rats conditioned to avoid L-Asp also avoided MSG. Conditioned aversions to MSG or L-Asp generalized to sucrose when amiloride was included in all solutions. Importantly, aversions to MSG or L-Asp did not generalize to NMDA, NaCl or KCl, and aversions to NMDA did not generalize to MSG, L-Asp, sucrose or KCl. These data indicate that rats perceive MSG and L-Asp as similar tastes, whereas NMDA, NaCl and KCl elicit other tastes. The results do not support a dominant role for the NMDA subtype of glutamate receptors in taste transduction for MSG (i.e. umami) in rats.     

Ontogenetic characteristics of the acquisition and extinction of a taste aversion in dogs following damage to the dorsal area of the hippocampus

In 2-9 months dogs the influence was studied of ablation of the hippocampus dorsal area on formation and preservation of conditioned taste aversion (CTA), elaborated by combination of 30% sucrose solution with i.p. injection of 0.28 M LiCl solution. Lesion of the hippocampus dorsal area does not prevent acquisition after the first pairing of conditioned taste aversion in puppies and adult dogs. Heterogeneous influences are observed after hippocampus lesions on the process of CTA extinction in animals of different ages. Acquaintance with conditioned stimulus before CTA acquisition accelerates the process of its extinction in hippocampectomized indiviuals, but less than in animals with an intact hippocampus.     

Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat

The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion.     

A conditioned aversion study of sucrose and SC45647 taste in TRPM5 knockout mice

Previously, published studies have reported mixed results regarding the role of the TRPM5 cation channel in signaling sweet taste by taste sensory cells. Some studies have reported a complete loss of sweet taste preference in TRPM5 knockout (KO) mice, whereas others have reported only a partial loss of sweet taste preference. This study reports the results of conditioned aversion studies designed to motivate wild-type (WT) and KO mice to respond to sweet substances. In conditioned taste aversion experiments, WT mice showed nearly complete LiCl-induced response suppression to sucrose and SC45647. In contrast, TRPM5 KO mice showed a much smaller conditioned aversion to either sweet substance, suggesting a compromised, but not absent, ability to detect sweet taste. A subsequent conditioned flavor aversion experiment was conducted to determine if TRPM5 KO mice were impaired in their ability to learn a conditioned aversion. In this experiment, KO and WT mice were conditioned to a mixture of SC45647 and amyl acetate (an odor cue). Although WT mice avoided both components of the stimulus mixture, they avoided SC45647 more than the odor cue. The KO mice also avoided both stimuli, but they avoided the odor component more than SC45647, suggesting that while the KO mice are capable of learning an aversion, to them the odor cue was more salient than the taste cue. Collectively, these findings suggest the TRPM5 KO mice have some residual ability to detect SC45647 and sucrose, and, like bitter, there may be a TRPM5-independent transduction pathway for detecting these substances.     

Genetic differences in nicotine-induced conditioned taste aversion

Genetic differences in nicotine-induced conditioned taste aversion were examined using inbred mice. Adult male C57BL/6J, DBA/2J, BALB/cJ and C3H/heJ mice were adapted to a 2-h per day water access regimen. Subsequently, mice received nicotine injections (0.5, 1.0 or 2.0 mg/kg) immediately after 1-h access to a NaCl flavored solution. DBA and C3H mice developed dosedependent aversions to the nicotine-paired flavor. BALB mice showed only minor reductions in intake with no difference between the nicotine dose groups. C57BL mice did not show development of nicotine-induced conditioned taste aversion. These results demonstrate that nicotine's aversive motivational effect is strongly influenced by genotype. Further, genetic sensitivity (DBA mice) or insensitivity (C57BL mice) to nicotine-induced conditioned taste aversion was similar to reports of genetic sensitivity to ethanol's aversive effect measured in this design.     

Oral cues involved in the rat's selective intake of fats

Food sensory preferences and aversions and therefore the selectiveintake of nutrients are conditioned by the post-ingestive nutritiveor deleterious effects of foods. Like the selective responseto carbohydrates is permitted by a common sweet taste, it couldbe suspected that a common fatty odor or a common greasy texturecould represent a "fat flavor" allowing the selective intakeof fats. The method of "illness-induced-aversion" was used ongroups of normal and anosmic rats. Rats were offered stock powdereddiet mixed with 20% of a fat (Butter B, Margarine M, VaselineV, Lard L) on the conditioning day and the same or differentfat on the test day. Results obtained in normal rats indicatedthat the conditioned aversion against L, B and M was generalizedfrom one to the others but it was not generalized to V. Resultsin anosmic compared to intact rats displayed that a proximityof the greasy texture of L, B and M and of the odor of B, M,V explains the various levels of generalization observed inintact rats. However the existence of a family of fatty odorswas not confirmed by the results.     

Generalization of specific taste aversions to alcohol in the rat

Two experiments were conducted to examine the taste qualitiesof alcohol in the rat. In Experiment 1, rats were trained toavoid sucrose, quinine or a sucrose + quinine mixture. In Experiment2, rats were trained to avoid sucrose, hydrochloric acid ora sucrose + hydrochloric acid mixture. In both experiments ratswere then tested for generalization to 3, 6 and 9% (v/v) alcoholsolutions. Following the alcohol tests rats were tested withthe taste solutions used during training. Results showed thatrats trained to avoid sucrose (Experiments 1 and 2), quinineor the sucrose + quinine mixture generalized that aversion tothe 6% alcohol solution. No generalization was found to the3% alcohol solution. No generalization was displayed by ratstrained to avoid either the hydrochloric acid solution or thesucrose + hydrochloric acid solution. Following the alcoholtests, all trained rats exhibited strong aversions to the solutionthey were trained to avoid. In addition, rats trained to avoida single solution generalized that aversion to the mixture andrats trained to avoid a mixture generalized to the single components.     

Conditioned taste aversion and motion sickness in cats and squirrel monkeys

The relationship between vomiting and conditioned taste aversion was studied in intact cats and squirrel monkeys and in cats and squirrel monkeys in which the area postrema was ablated by thermal cautery. In cats conditioned 7-12 months after ablation of the area postrema, three successive treatments with xylazine failed to produce either vomiting or conditioned taste aversion to a novel fluid. Intact cats, however, vomited and formed a conditioned aversion. In squirrel monkeys conditioned 6 months after ablation of the area postrema, three treatments with lithium chloride failed to produce conditioned taste aversion. Intact monkeys did condition with these treatments. Neither intact nor ablated monkeys vomited or evidenced other signs of illness when injected with lithium chloride. When the same ablated cats and monkeys were exposed to a form of motion that produced vomiting prior to surgery, conditioned taste aversion was produced and some animals vomited. These findings confirm other studies indicating motion can produce vomiting in animals with the area postrema destroyed and demonstrate that motion-induced conditioned taste aversion can be produced after ablation of the area postrema. The utility of conditioned taste aversion as a measure of subemetic motion sickness is discussed by examining agreement and disagreement between identifications of motion sickness by conditioned taste aversion and vomiting. It is suggested that a convincing demonstration of the utility of conditioned taste aversion as a measure of nausea requires the identification of physiological correlates of nausea, and caution should be exercised when attempting to interpret conditioned taste aversion as a measure of nausea.     

咸味觉厌恶模型大鼠鼓索神经对味觉刺激的电生理反应特性

目的:探索大鼠咸味觉厌恶建立后外周鼓索神经(CT)对咸味觉及其他味觉刺激的电生理反应特性的改变。方法:将14只SD成年雄性大鼠分为咸味觉厌恶模型组(CTA)和对照组(n=7/group)。实验第1日给予大鼠30min的0.1mol/LNaCl饮食,随后CTA组和对照组大鼠分别腹腔注射2ml0.15mol/LLiCl和同等量生理盐水。在第2、3和4日,测量两组大鼠每天30min内对NaCl和蒸馏水饮用量。于第4日行为学测试后,分别记录CTA组大鼠和对照组大鼠CT对口内给予系列浓度NaCl溶液、0.3mol/LNaCl与0.1mmol/L阿米洛利(一种舌上皮钠通道阻断剂)混合液和其他四种基本味觉刺激溶液的电生理反应。结果:与对照组相比,CTA组大鼠CT对系列浓度NaCl和其他4种基本味觉刺激的电生理反应特性没有发生明显变化(P>0.05);舌上皮钠通道阻断剂阿米洛利强烈抑制CTA大鼠对NaCl的反应(P<0.01)。结论:条件性咸味觉厌恶模型大鼠CT对各种味觉刺激的电生理反应特性没有发生明显改变。     

Dose-dependent effects of peptide YY(3-36) on conditioned taste aversion in rats

We used a conditioned taste aversion test to assess whether PYY(3-36) reduces food intake by producing malaise. Two-hour IV infusion of PYY(3-36) (8, 15, and 30 pmol/kg/min) at dark onset in non-food-deprived rats produced a dose-dependent inhibition of feeding and a conditioned aversion to the flavored chow paired with PYY(3-36) infusion. In food-deprived rats, PYY(3-36) at 2 and 4 pmol/kg/min inhibited intake of a flavored saccharin solution without producing conditioned taste aversion, whereas higher doses (8 and 15 pmol/kg/min) inhibited saccharin intake and produced taste aversion. These results suggest that anorexic doses of PYY(3-36) may produce a dose-dependent malaise in rats, which is similar to that reported for PYY(3-36) infusion in humans. Previous studies have shown that PYY(3-36) potently inhibits gastric emptying, and that gut distention can produce a conditioned taste aversion. Thus, PYY(3-36) may produce conditioned taste aversion in part by slowing gastric emptying.     

Long-delay learning in rats with parabrachial pontine lesions

Two experiments were conducted to test the hypothesis that ratswith lesions in the parabrachial nucleus of the pons (PbN) canacquire conditioned taste aversions only if the conditionedand unconditioned stimuli are presented close together in time.In experiment 1, rats with lesions in the medial PbN, lateralPbN or outside of the PbN (lesioned control), and unoperatedcontrol rats were trained to avoid Na-saccharin in a one-bottletest. In this procedure, a 5-min delay was imposed between the15-min Na-saccharin presentation and an injection of LiCl (0.3M, 1 % body weight, i.p.). Results showed that, after threeNa-saccharin-LiCl pairings, all rats, except the medial PbNgroup, acquired a strong aversion to Na-saccharin. In experiment2, the same rats were presented with LiCl (0.12 M) in their15-min daily access to fluid on 3 alternate days. Although ratsin the medial PbN group drank more LiCl on day 1 than rats inthe other groups, they significantly reduced their LiCl consumptionon day 2 and did not differ from other groups by day 3. Resultsare discussed in terms of possible behavioral and physiologicalmechanisms that might account for these phenomena.