Conditioned and unconditioned defensive burying in the rat

When rats first encountered a mouse-trap or a flashbulb in a chamber to which they had been habituated, they buried it with bedding material from the floor of the chamber, whereas rats previously habituated to the trap or the flashbulb did not. Conversely, rats did not bury a stationary, wire-wrapped wooden prod or a length of polyethylene tubing, even on first encounter. However, almost every rat struck by the trap, shocked by the prod, exposed to an airblast from the tube, or to a flash of the bulb, buried the respective source of aversive stimulation with the bedding material, even when a comparable control object was present during conditioning and testing. Thus, the phenomenon of defensive burying is not restricted to situations in which neutral objects serve as the source of painful electric shock. Rats seem to enter the experimental environment with an already established tendency to bury some objects (unconditioned defensive burying) but not others, and they readily learn to selectively bury an object that has been the source of any one of a variety of aversive stimuli (conditioned defensive burying).     

Rat defensive behavior: burying noxious food.

In Experiment 1, rats living in chambers containing bedding material were injected with a toxicosis-producing dose of lithium chloride shortly after their initial taste of sweetened condensed milk. They consumed no additional milk and used the bedding to bury the spout through which the milk had been delivered, although they did not bury a concurrently available water spout. In another control condition, rats did not bury a spout containing a novel solution (saccharin) not paired with toxicosis. In Experiment 2, rats did not bury a milk spout until milk consumption was followed by toxicosis. In Experiment 3, rats buried a spout containing Tabasco pepper sauce but not a concurrently available water spout. Thus, burying the food source appears to be an integral component of the rat's defensive reaction to noxious food.     

Defensive burying of aversive fluids in rats: The effects of peripheral anosmia

Three experiments were conducted in order to determine the role of olfactory stimulation in defensive burying of aversive fluids in rats. The results revealed that zinc sulfate-induced anosmia eliminated burying of fluids paired with lithium chloride as well as an inherently aversive solution. This occurred despite the fact that the rats avoided consuming them. These data indicate that defensive burying of aversive fluids is governed by olfactory stimuli and confirms an earlier report, which indicted that burying does not occur in response to aversive gustatory stimuli.     

Characterization of a dose-response curve for nicotine-induced conditioned taste aversion in rats: relationship to elevation of plasma beta-endorphin concentration

In the first experiment a conditioned taste aversion paradigm was used to characterize a dose-response curve for the aversive properties of nicotine in male Sprague-Dawley rats. Doses of nicotine ranging from 0.01 to 0.46 mg/kg, 2.0 ml of 0.47 M lithium chloride, or saline were injected, ip, 10 min after exposure to a novel saccharin solution. Amount of saccharin consumed in a two-bottle test was assessed 72 h later. Nicotine doses of 0.046 mg/kg and above produced a significant degree of conditioned taste aversion. In a second experiment, four groups of 10 rats each were injected with saline, 0.022 mg/kg nicotine, 0.46 mg/kg nicotine, or 2.0 ml 0.47 of M LiCl. Doses of 0.46 mg/kg nicotine and 0.47 M LiCl elevated plasma beta-endorphin concentrations significantly above saline control values. The 0.022 mg/kg dose, the highest dose that did not produce conditioned taste aversion in Experiment 1, did not significantly increase plasma beta-endorphin concentrations. This finding suggests that doses of nicotine that produce conditioned taste aversion also promote the release of pituitary stress hormones. Taken together these data suggest that some of the pharmacological and behavioral effects attributed to nicotine, including the release of endogenous neuromodulators, may be dose-dependent concomitants of the aversive effects of nicotine in nicotine-naive animals.     

On the nature of processes governing defensive burying of aversive flavors and odors in rats

Four experiments are reported which investigated the processes which contribute to the failure of rats to bury fluids that have acquired aversive properties through pairings with lithium chloride toxicosis. Fluids that failed to provide strong olfactory stimulation were avoided but not buried. These solutions, however, produced higher order conditioning of odor-bearing solutions which were buried readily. Various control experiments indicated that these effects depended upon the odorous qualities of the stimulus and not upon simple novelty effects or changes in gustatory stimulation. These data indicate that the inability of aversive gustatory cues to produce burying reflects a constraint on motivational or S-R learning processes.     

Defensive burying of aversive fluids in rats: The possible role of odor

Defensive burying of flavored fluids paired with lithium chloride injections was examined. Rats showed little inclination to bury conditioned saccharin or salt solutions (Experiments 1 and 2). However, they buried tabasco sauce or dilute milk solutions readily (Experiment 3). It was hypothesized that the amount of olfactory stimulation provided by a solution may determine whether a rat engages in burying. This hypothesis received support in a final experiment which demonstrated that rats readily buried an arbitrarily selected odorous solution which was previously paired with lithium chloride. Thus the present experiments begin the process of identifying the circumstances under which burying does and does not occur.     

Cholinergic dependence of taste memory formation: evidence of two distinct processes

Learning the aversive or positive consequences associated with novel taste solutions has a strong significance for an animal's survival. A lack of recognition of a taste's consequences could prevent ingestion of potential edibles or encounter death. We used conditioned taste aversion (CTA) and attenuation of neophobia (AN) to study aversive and safe taste memory formation. To determine if muscarinic receptors in the insular cortex participate differentially in both tasks, we infused the muscarinic antagonists scopolamine at distinct times before or after the presentation of a strong concentration of saccharin, followed by either an i.p. injection of a malaise-inducing agent or no injection. Our results showed that blockade of muscarinic receptors before taste presentation disrupts both learning tasks. However, the same treatment after the taste prevents AN but not CTA. These results clearly demonstrate that cortical cholinergic activity participates in the acquisition of both safe and aversive memory formation, and that cortical muscarinic receptors seem to be necessary for safe but not for aversive taste memory consolidation. These results suggest that the taste memory trace is processed in the insular cortex simultaneously by at least two independent mechanisms, and that their interaction would determine the degree of aversion or preference learned to a novel taste.     

NMDA and muscarinic receptors of the nucleus accumbens have differential effects on taste memory formation

Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent presentations (attenuation of neophobia, AN). It has been shown that the nucleus accumbens (NAcc) has an important role in taste learning. To elucidate the involvement of N-methyl-D-aspartate (NMDA) and muscarinic receptors in the NAcc during safe and aversive taste memory formation, we administrated bilateral infusions of DL-2-amino-5-phosphonopentanoic acid (APV) or scopolamine in the NAcc shell or core respectively. Our results showed that pre-training injections of APV in the NAcc core and shell disrupted aversive but not safe taste memory formation, whereas pre-training injections of scopolamine in the NAcc shell, but not core, disrupted both CTA and AN. These results suggest that muscarinic receptors seem to be necessary for processing taste stimuli for either safe or aversive taste memory, whereas NMDA receptors are only involved in the aversive taste memory trace formation.     

ACTH and ACTH4-10 modification of neophobia and taste aversion responses in the rat.

A series of experiments assessed the effects of ACTH and the ACTH analogue ACTH4-10 on drinking in conditioned taste aversion and neophobic situations. Both substances delayed the extinction of a conditioned taste aversion established by a single pairing of lithium chloride with milk (Experiment 1). However, in this situation, the ACTH parent peptide was more potent behaviorally. Administration of ACTH suppressed milk consumption in animals with no toxicosis experience (Experiment 2). This effect was apparently not due to the conditioning of a taste aversion (Experiment 3) with ACTH serving as a weak aversive unconditioned stimulus. Administration of exogenous ACTH (Experiment 4) or ACTH4-10 (Experiment 5) did not enhance neophobia; however, repeated injections of ACTH suppressed drinking. This ACTH suppression was related to the familiarity/novelty of the subtance being consumed. The neophobic response to milk eas no accompanied by pituitary-adrenal activation (Experiment 6). Both neophobic and conditioned taste aversion situation appear to be useful for assessing peptide effects on consummatory behavior.     

Conditioned taste and taste-potentiated odor aversions in the Syracuse high- and low-avoidance (SHA/Bru and SLA/Bru) strains of rats (Rattus norvegicus).

Syracuse high- and low-avoidance Long-Evans rats (Rattus norvegicus; SHA/Bru and SLA/Bru) were selectively bred for good and poor active-avoidance learning. However, SLA/Bru animals are superior to SHA/Bru rats in conditioned suppression and passive avoidance learning. In this experiment, saccharin taste and almond odor were the components of a compound conditioned stimulus (flavor) in an illness-induced aversive conditioning paradigm. SLA/Bru rats (n = 17) showed stronger conditioned flavor, taste, and odor aversion than did SHA/Bru animals (n = 18). Unselected Long-Evans rats (n = 18) were intermediate between the selected strains. SLA/Bru and Long-Evans rats showed taste-potentiated odor aversions in this experiment, whereas SHA/Bru animals did not. The results provide evidence that genetic factors, as exemplified by the different strains, are importantly involved in the mechanisms underlying interoceptive and exteroceptive aversive conditioning.     

Species-typical taxic behavior and event-reinforcer interactions in conditioning

The role of species-typical taxic behavior in conditioning was studied using thigmotaxis (wall hugging) in rats. Running toward or staying near walls in an open-field apparatus was assumed to be compatible with the rat's defensive behavior, and running to or staying in open spaces was assumed to be incompatible. With large food rewards no differences between the center and side responses were found in acquisition under continuous or intermittent reward, but the center response showed greater suppression after contingent punishment was applied on nonreward trials. Two additional experiments showed that differences between center and side responses occur during extinction when avoidance of shock but not when food is the reinforcer. The results suggest that instances of response-reinforcer interactions may be predicted by knowledge of species-typical defensive behavior and that reactions elicited by shock are not always identical to those elicited by frustration in their consequences for the performance of conditioned behavior.     

条件性味觉厌恶分化后臂旁核c-fos表达的变

以口内注入糖精或蔗糖溶液为条件刺激,腹腔内注射LiCl为非条件刺激,在大鼠形成条件性味觉厌恶后进行分化训练,观察味质和嗜好性对臂旁核各亚核c-fos表达的影响及其交互作用。结果表明：味质和嗜好性对背侧外侧亚核(dls)和腹侧外侧亚核(vls)的c-fos表达无影响;在内侧外侧亚核(ils)和外部内侧亚核(ems),蔗糖诱导的c-fos表达高于糖精,但在外部外侧亚核(els),糖精诱导的表达高于蔗糖;嗜好性刺激引起ils、中央外侧亚核(cls)和cms内c-fos高表达,厌恶性刺激引起ems和els内的高表达。在ils和cms嗜好性与味质的影响各自独立,在els和ems内嗜好性与味质的影响存在交互作用。提示PBN内存在味质辨别和报酬评价的代表区,两种代表区有交迭,ems和els对味质信息和报酬信息的整合有重要作用     

The effect of prior acquisition of food aversion on the poisoned‐partner effect

It has been suggested that poisoned conspecifics function as aversive unconditioned stimuli for rats. The present study examined whether the prior acquisition of food aversion could enhance this effect. In phase 1, subjects were given pairings of cocoa‐flavored pellets and a toxin. In phase 2, they were given the cocoa‐flavored pellets and later presented with a poisoned or nonpoisoned conspecific. Subsequent testing involved a choice between the cocoa‐flavored pellets and regular pellets. Prior exposure to a poisoned conspecific prevented extinction of the conditioned aversion. In contrast, exposure to a nonpoisoned conspecific allowed extinction of the conditioned aversion. These findings suggest that a rat's reaction to a stressed conspecific is affected by their prior experience of aversive events.     

Flavor-illness aversions: potentiation of odor by taste is disrupted by application of novocaine into amygdala

Taste and odor have different properties in toxiphobic conditioning. When each is used alone, taste becomes aversive when followed by immediate or delayed poison, while odor becomes aversive only if followed by immediate poison. However, if odor and taste are presented as a compound and followed by delayed poison, then odor does become aversive when tested alone. It is as if taste has potentiated the odor signal. Several experiments assessed the role of the amygdala in this potentiation effect by anesthetizing the amygdala with 10% novocaine. Novocaine applied 30 min before presentation (Pre-CS) of an odor-taste compound disrupted the potentiated odor aversion but not the taste aversion. In contrast, novocaine applied 1 min after the compound odor-taste or 1 min prior to LiCl poison did not dissociate odor and taste aversions; both odor and taste aversions were facilitated. Novocaine applied 30 min before an odor alone also disrupted an odor aversion induced by immediate LiCl. But identical treatment did not disrupt odor avoidance conditioned by immediate foot-shock, suggesting that amygdala anesthesia does not simply produce anosmia. Pre-CS novocaine treatment also disrupted flavor neophobia prior to conditioning. The results suggest that novocaine applied to the amygdala disrupts the integration of odor with taste and illness during toxiphobic conditioning.     

以兔抗鼠淋巴细胞血清为非条件刺激的条件性免疫抑制

采用一种生物类免疫抑制剂-兔抗鼠淋巴血清（rabbit anti-rat lymphocyte serum,ALS）为非条件刺激（UCS）,糖精水为条件刺激（CS）,以双瓶给水法置于鼠笼前端饮用偏好侧。在一次性CS-UCS结合训练后,单独再次给予CS,使卵清蛋白（OVA）免疫过的大鼠表现出脾淋巴细胞对有丝分裂原PWM的增殖反应降低,血抗OVA抗体的总量及脾内抗OVA抗体生成细胞的减少,但动物未表现出条件性味觉厌恶的行为反应。这些结果表明条件性免疫抑制与味觉厌恶行为条件反射没有必然联系,并非是厌恶行为反应或情绪应激的伴随产物。UCS也并非必需具有感觉的毒副作用,条件性免疫抑制是脑高级神经活动调节免疫功能的结果。     

Temporary basolateral amygdala lesions disrupt acquisition of socially transmitted food preferences in rats

Lesions of the basolateral amygdala (BLA) have long been associated with abnormalities of taste-related behaviors and with failure in a variety of taste- and odor-related learning paradigms, including taste-potentiated odor aversion, conditioned taste preference, and conditioned taste aversion. Still, the general role of the amygdala in chemosensory learning remains somewhat controversial. In particular, it has been suggested that the amygdala may not be involved in a form of chemosensory learning that has recently received a substantial amount of study-socially transmitted food preference (STFP). Here, we provide evidence for this involvement by pharmacologically inactivating the basolateral amygdala bilaterally during STFP training. The same inactivation sites that impaired taste aversion learning eliminated the normally conditioned preference for a food smelled on a conspecific's breath. Impairments of learned preference persisted even in testing sessions in which BLA was not inactivated, and learning was normal when the BLA was inactivated only during testing sessions; thus, the impairment was a true acquisition deficit. In conjunction with previous results from other paradigms, therefore, our data suggest that the amygdala is vital for learning procedures involving pairings of potent and arbitrary chemosensory stimuli.     

Taste preconditioning augments odor-aversion learning

On the basis of previous work that has shown a taste can potentiate odor-aversion conditioning in AX+ conditioning, 6 experiments used rats to examine the effects of pairing a preconditioned taste (A) with a novel odor cue (X) in an A+/AX+ aversion conditioning design. Experiments 1A and 1B demonstrated that a preconditioned taste produced a robust odor aversion that was significantly stronger than a potentiated odor aversion. The results of Experiment 2 showed that the robust odor aversion produced by A+/AX+ conditioning was not the result of the potentiated odor aversion summating with generalization from the taste aversion. The augmented odor aversion was produced only when the taste and odor stimuli were presented simultaneously (Experiment 3) and the preconditioned taste aversion was intact at compound conditioning (Experiment 4). Pairing a novel odor with a preconditioned taste was not sufficient to condition an aversion to odor (Experiment 5), although other results implicated a role for an association between odor and taste in the odor augmentation effect (Experiment 6). The present results have implications for current models of taste + odor interactions in flavor-aversion conditioning.     

Intracellular calcium chelation and pharmacological SERCA inhibition of Ca2+ pump in the insular cortex differentially affect taste aversive memory formation and retrieval

Variation in intracellular calcium concentration regulates the induction of long-term synaptic plasticity and is associated with a variety of memory/retrieval and learning paradigms. Accordingly, impaired calcium mobilization from internal deposits affects synaptic plasticity and cognition in the aged brain. During taste memory formation several proteins are modulated directly or indirectly by calcium, and recent evidence suggests the importance of calcium buffering and the role of intracellular calcium deposits during cognitive processes. Thus, the main goal of this research was to study the consequence of hampering changes in cytoplasmic calcium and inhibiting SERCA activity by BAPTA-AM and thapsigargin treatments, respectively, in the insular cortex during different stages of taste memory formation. Using conditioned taste aversion (CTA), we found differential effects of BAPTA-AM and thapsigargin infusions before and after gustatory stimulation, as well as during taste aversive memory consolidation; BAPTA-AM, but not thapsigargin, attenuates acquisition and/or consolidation of CTA, but neither compound affects taste aversive memory retrieval. These results point to the importance of intracellular calcium dynamics in the insular cortex during different stages of taste aversive memory formation.     

Inferior olive lesions impair concurrent taste aversion learning in rats.

Taste aversion learning can be established according to two different procedures, concurrent and sequential. For the concurrent task, two different taste stimuli are offered at the same time, one associated with simultaneous intragastric administration of an aversive stimulus and the other associated with physiological saline. This discrimination is learned by sham-lesioned control animals and by animals with lesions in the cerebellar cortex but not by rats lesioned in the inferior olive. At the same time, animals with lesions in the inferior olive and sham-lesioned animals achieve sequential learning when the gustatory stimuli are offered individually during each daily session. The results obtained show that electrolytic lesions in the inferior olive impair acquisition of concurrent learning and are analyzed in terms of an anatomical system consisting of the vagus nerve, inferior olive, and cerebellum, which differentiates between the two modalities of taste aversion learning, concurrent and sequential.     

Does Conspecific Fighting Yield Conditioned Taste Aversion in Rats?

Running in an activity wheel yields conditioned aversion to a taste solution consumed before the running, but its underlying physiological mechanism is unknown. According to the claim that energy expenditure or general stress caused by physical exercise is a critical factor for this taste-aversion learning, not only running but also other stressful exercises should yield conditioned aversion to the paired taste. This prediction was disconfirmed in two experiments, because stressful conspecific fighting did not work as an effective agent to establish taste aversion in rats.