Attenuation of x-ray-induced taste aversions by olfactory-bulb or amygdaloid lesions

These experiments used Sprague-Dawley derived rats to study the effects of either olfactory-bulb or amygdaloid lesions on x-ray-induced taste aversions. Sham-operated and normal subjects exposed to 60 roentgens of x-radiation following saccharin ingestion developed marked saccharin aversions while sham-irradiated controls maintained strong saccharin preferences. Olfactory-bulb lesions supported reports that bulbectomies can partially disrupt the acquisition of x-ray-induced saccharin aversions. Suggestive evidence of similar aversion disruption was also observed following amygdaloid lesions. A second experiment which produced stronger aversions showed that amygdaloid lesions can impair the acquisition of x-ray-induced saccharin aversions. This experiment also confirmed that bulbectomized subjects do develop significant aversions under appropriate conditioning parameters. Olfactory-bulb lesions approximated total bulbectomies while amygdaloid lesions were centered in the corticomedial amygdala with some damage to basolateral nuclei. Bulbectomy results are discussed in relation to nonsensory contributions of the olfactory bulbs. Amygdaloid lesions are related to possible contributions of different amygdaloid regions.     

Conditioned aversion to a taste perceived while grooming

Four experiments were conducted to determine how the characteristics of conditioned taste aversion (CTA), as described from studies conducted in the drinking and feeding contexts, applied in the grooming context. In Experiment 1, sodium saccharin was mixed with a "neutral-tasting" jelly and applied to the fur of male Sprague-Dawley rats. Rats injected with LiCl after the applications strongly avoided saccharin solutions in subsequent 1-hr, 2-choice (Saccharin solution vs water) drinking tests, whereas rats injected with NaCl or given plain jelly on the fur showed only an initial neophobic response to the saccharin solution. Thus, the taste of saccharin was perceived while grooming and the CTA formed in the grooming context generalized to drinking. In experiments 2-4, we obtained evidence that: (a) rats discriminated between one intensity of saccharin applied to the fur and another used in the test solution; and (b) rats differentiated between qualities of the two tastants applied to the fur in that saccharin overshadowed NaCl; and (c) taste qualities were more important than toxic properties when two stimuli (Saccharin, LiCl) were used (saccharin overshadowed NaCl in subsequent drinking tests). We speculate that taste, while grooming might play a role in social communication in some vertebrates. Further, CTA and grooming might have uses in rodent control (e.g., in agricultural situations) not previously considered such as in delivering a non-attractive, low-salience toxin so that the taste of the crop overshadows that of the bait, and induces crop aversion.     

Interactions of temperature and taste in conditioned aversions

The influence of temperature on taste cues and the ability to discriminate and learn about different temperatures of foods are important factors regulating ingestion. The goal of this research was to demonstrate that thermal orosensory input can serve as a salient stimulus to guide ingestive behavior in the rat, and also that it interacts with gustatory input during choice and conditioned aversion experiments. A novel apparatus with Peltier refrigerators was used to control the temperature of solutions in 10-min, 2-bottle tests. It was determined that naive rats preferred cold water (10 °C) to warm water (40°). When cold water was paired with a toxic LiCl injection, rats avoided cold water and drank warm water, thus demonstrating that cold water could serve as the conditioned stimulus in a conditioned temperature aversion. Rats conditioned against cold water could discriminate 10 °C water from 16 °C water, but not from 13 °C water, thus showing an ability to discriminate orosensory thermal cues to within 3-6 °C. Rats also generalized conditioned aversions from cold water to cold saccharin and cold sucrose solutions. However, if rats were conditioned against a compound taste and thermal stimulus (10 °C, 0.125% saccharin), the rats could distinguish and avoid each component individually, i.e., by avoiding cold water or warm saccharin. Finally, daily 2-bottle extinction tests were used to assess the strength of aversions conditioned against a taste cue (0.25 M sucrose), a thermal cue (10 °C water), or the combination. Aversions to taste or temperature alone persisted for 7-14 days of extinction testing, but the combined taste-temperature aversion was stronger and did not extinguish after 20 days of extinction testing. These results demonstrate that temperature can serve as a salient cue in conditioned aversions that affect ingestion independent of taste cues or by potentiating taste cues.     

Effects of swim stress on latent inhibition using a conditioned taste aversion procedure

Rats were used to examine the effects of inescapable swim stress on latent inhibition using a conditioned taste aversion procedure. Subjects were subjected to inescapable swim after each of three saccharin taste preexposures and saccharin was later paired with LiCl. The ability of swim to influence latent inhibition was assessed on subsequent saccharin test trials. Swim stress significantly attenuated latent inhibition. The implications of these results regarding the effects of swim stress on conditioned taste aversion are discussed.     

Conditioned taste aversion suppresses induction of delayed-type hypersensitivity immune reactions

Conditioned taste aversion was induced in mice by pairing saccharin drinking with an intraperitoneal injection of lithium chloride, a toxic but nonimmunosuppressive drug. Conditioned mice showed not only suppressed saccharin drinking but also a 75% reduction in the induction of delayed-type hypersensitivity immune responses to low doses of sheep erythrocytes. This effect was observed with doses of lithium chloride which had no effect of their own on immune functions. In addition, a reduction in water consumption was not responsible for the reduced immune response of conditioned mice since the immune responses of water deprived mice did not differ from those of nondeprived mice. Conditioned mice exposed to saccharin had higher plasma levels of glucocorticoids than nonconditioned mice, suggesting that the experience of being reexposed to a taste paired with lithium chloride was perceived as aversive. These data demonstrate that alterations in immune functions can be induced by a conditioned taste aversion procedure independently of any immunosuppressive drug.     

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.     

Attenuation of ethanol-induced conditioned taste aversion by naloxazone: behavioral evidence for an opiate receptor-mediated morphine-ethanol interaction

When rats are presented with a novel saccharin solution and immediately injected with either morphine or ethanol, they subsequently develop a conditioned taste aversion (CTA) to the saccharin solution which reflects the aversive component of the conditioning drug. The present study provides evidence which suggests that both morphine-induced and ethanol-induced CTAs can be blocked by the specific high-affinity binding opiate antagonist, naloxazone.     

Comparative effects of lesion of the basolateral nucleus and lateral nucleus of the amygdaloid body on neophobia and conditioned taste aversion in the rat

The effects of bilateral lesions of the basolateral and lateral nuclei of the amygdala on the neophobic response and LiCl-conditioned taste aversion to a saccharin solution were studied in rats. Compared to intact animals, rats with basolateral lesions did not exhibit neophobia to the novel stimulus, while rats with lateral lesions demonstrated an initial preference to the sweet solution over water. The LiCl-induced aversion was suppressed after basolateral lesions and was unchanged after lateral lesions. It is concluded that these two amygdaloid nuclei play an important but distinct role in neophobia and conditioned taste aversion.     

Kindling increases aversion to saccharin in taste aversion learning

Kindling is a model in which an initially subconvulsive electrical stimulation of certain brain areas eventually develops a generalized seizure that produces behavioral and long term neuronal changes. In the present study we evaluated if kindling can modify conditioning taste aversion (CTA). In this paradigm animals acquire aversion to saccharin when it is presented as the conditioned stimulus (CS) followed by an injection of lithium chloride (LiCl) that induces a gastric irritation as the unconditioned stimulus (US). Male Wistar rats were implanted with bipolar electrodes aimed at the right amygdala (AMG) or at the right insular cortex (IC). The animals were stimulated daily until they reached stages 2-4 (intermediate) or until kindling was fully established (three consecutive stage 5 seizures). At least two weeks after kindling stimulation had ceased the animals were deprived of water for 24 h and given 10-min drinking sessions twice a day for 4 days. On day 5 (morning session) tap water was replaced by saccharin solution (0.1%), 20 min later the animals were injected with LiCl (7.5 ml/kg i.p., 0.2 M) to induce gastric malaise or taste aversion. After three more days of baseline consumption, water was substituted by a fresh 0.1% saccharin solution to test the aversion. AMG-kindling delayed the extinction of CTA. Animals with kindling in the IC had a higher retention than the sham kindling group; that is, they drank significantly less saccharin solution than the other groups. The results of the present experiment show that local modification of brain function induced by kindling stimulation can prolong the aversive effects of CTA.     

Differential effect of paradoxical sleep deprivation on acquisition and retrieval of conditioned taste aversion in rats.

Paradoxical sleep deprivation (PSD) was used to interfere with acquisition or retrieval of conditioned taste aversion (CTA). PSD was achieved by confining rats to small pedestals placed on an electrified grid floor. Fifteen-min access to 0.1% sodium saccharin (conditioned stimulus-CS) by water deprived rats was followed 30–120 min later by intraperitoneal injection of lithium chloride (unconditioned stimulus-US, 0.15 M, 2% to 4% body weight). Retention was tested 1 to 5 days later by offering the animal saccharin again. A 24-hr PSD preceding saccharin drinking prevented CTA acquisition. CTA disruption was diminished by a 2-hr, and completely abolished by an 8-hr interval of home cage recovery inserted between the 24-hr PSD and saccharin presentation. CTA was slightly facilitated by 2-hr PSD in the CS-US interval. The 24-hr PSD preceding CS caused the same CTA disruption when followed by free sleep opportunity or by continued PSD in the 2-hr CS-US interval. Twenty-four-hr PSD preceding retention testing slightly improved retrieval of well established CTA. It is concluded that PSD interferes with the formation of the short-term gustatory trace of CTA but does not affect retrieval of CTA engrams. Gradual compensation for the PSD effect on CTA learning by pre-acquisition sleep suggests that the processes responsible for CTA disruption and recovery correspond to depletion and repletion of the same neurotransmitter stores.     

Amygdalectomy induced deficits in conditioned taste aversion: possible pituitary-adrenal involvement

Bilateral lesions to the amygdala in rats impaired a conditioned taste aversion produced by pairing the taste of sweetened milk with lithium chloride (Experiment 1). A second experiment investigated the role of adrencorticotropin (ACTH) in the amygdala lesion-induced deficits in conditioned taste aversion. ACTH injection on the day of conditioning was without effect in either sham or amygdala lesioned animals. ACTH injection on the day of testing was without an effect in sham animals. However, ACTH injection augmented the avoidance behavior of amygdala lesioned subjects (Experiment 2). These data suggest a pituitary-adrenal involvement in the amygdalectomy-induced deficits in conditioned taste aversion.     

Effects of central amygdaloid nucleus lesions on ingestion, taste reactivity, exploration and taste aversion.

Central amygdaloid nucleus lesions in rats had no effect on recovery of preoperative body weight and food consumption levels. The brain damaged rats also recovered preoperative levels of water consumption as rapidly as control rats but then developed a mild but persistent hypodipsia. The experimental rats also drank less than control rats when food deprived and showed marginally reliable decreases in 0.1% quinine solution consumption and latency to consume a novel food. There was no detectable lesion effect on 0.1% saccharin solution consumption, exploration of a novel environment or formation of a learned taste aversion. It is suggested that the central amygdaloid nucleus has a role in mediating the relationship between food and water intake and in some taste mediated consummatory behavior.     

Sucrose taste but not Polycose taste conditions flavor preferences in rats

Rats have an inborn preference for sweet taste and learn to prefer flavors associated with sweetness. They are also strongly attracted to the taste of glucose polymers (e.g., Polycose). This "poly" taste differs in quality from the sweet taste of sugar. To determine if poly taste, like sweet taste, conditions flavor preferences rats were trained with a distinctive flavor (CS+) added to 2% Polycose solution and a different flavor (CS-) added to plain water. In a subsequent two-bottle test the rats did not prefer the CS+ to CS- when both flavors were presented in water. In contrast, other rats significantly preferred a CS+ flavor that had been paired with 2% sucrose. Adding saccharin to a flavored Polycose solution did not improve CS+ flavor learning; rather, Polycose appeared to overshadow saccharin-induced conditioning. Flavor conditioning by a 16% Polycose solution was assessed using a sham-feeding procedure to prevent post-oral reinforcement. Although the rats sham-fed substantial amounts of the CS+ flavored Polycose solution, they failed to prefer the CS+ to the CS- flavor. This contrasts with the preference other rats displayed for a CS+ paired with sham-fed sucrose. Why attractive sweet and poly tastes differ in their ability to condition flavor preferences is not certain, although some findings suggest that they differentially activate dopamine and/or serotonin circuits involved in flavor learning.     

Electroconvulsive shock impedes association formation: conditioned taste aversion paradigm

Rats injected with a toxic solution of lithium chloride (US) 30 min after drinking saccharin flavored water (CS) learned to avoid that taste upon subsequent encounter unless electroconvulsive shock (ECS) was administered immediately after the injection of US and, therefore, functionally during the CS-US interval. ECS delayed only 5 min after the US had no effect on conditioning while it is known to be disruptive if interpolated at any time up to 4 hr before the US (i.e., during the CS-US interval). The results suggested that ECS acts more effectively to prevent the occurrence of associative learning than to induce retrograde amnesia for an already formed association.     

Age‐dependent differences in morphine‐induced taste aversions

Adolescence is a developmental period of particular importance given the host of neurobiological changes that occur during this stage of development. Drug use and abuse is said to be a function of the balance of its rewarding and aversive effects, and any age‐dependent differences in morphine's aversive effects could impact drug intake. The present experiments examined the ability of morphine sulfate (0, 3.2, 10, and 18 mg/kg) to induce taste aversions in adolescent and adult rats under high (20‐min fluid access each day; Experiment 1A/B) and low (50% of ad libitum access; Experiment 2A/B) deprivation conditions. In both studies, adolescent and adult rats were given a novel saccharin solution to drink and were subsequently injected with morphine. Independent of the deprivation condition, adults acquired stronger aversions than adolescents and did so at a faster rate. On a subsequent two‐bottle aversion test, all morphine‐injected subjects drank a significantly lower percentage of saccharin than vehicle‐injected controls with adults exhibiting stronger aversions than adolescents. These age‐dependent differences in morphine‐induced CTAs extend the findings with other drugs of abuse for which adolescents exhibit weaker aversions. The possible basis for and implications of these differences were discussed. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 415–428, 2013     

Effects of desglycinamide-lysine vasopressin on a conditioned taste aversion in rats

Vasopressin and other pituitary peptides have been shown to increase resistance to extinction of active and passive shock-avoidance responses. Both paradigms use external cues as warning and punishing stimuli. The present work asked if a variant of vasopressin would have a similar effect on conditioned taste aversions (CTA), which use internal cues as warning and punishing stimuli. Eight groups of rats were defined by factorial combination of Pretreatment during Neophobia and Conditioning (vasopressin vs saline), UCS during Conditioning (pairing saccharin-flavored water with injections of lithium chloride or saline), and Pretreatment during Extinction (vasopressin vs saline). Rats given three saccharin-lithium pairings developed strong aversions. Of the rats with CTAs, those given vasopressin during conditioning, extinction, or both showed increased resistance to extinction on the last four of eight extinction days. Vasopressin had no other effect on drinking of saccharin. Vasopressin thus appears to enhance resistance to extinction of avoidance responses in both external and internal milieus.     

Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer's disease

Research into the underlying mechanisms of cognitive dysfunction in Alzheimer's disease (AD) has relied traditionally on tasks such as the water maze which evaluate spatial learning and memory. Since non-spatial forms of memory are also disrupted by AD, it is critical to establish other paradigms capable of investigating these deficits. Utilizing a non-spatial learning task, acquisition of conditioned taste aversion (CTA) was evaluated in a mouse model of AD. This line of transgenic mice encode a mutated allele of the human amyloid precursor protein (APP) and presenilin 1 (PS1) genes and exhibit extensive amyloid plaque deposition in the brain by 6-7 mo of age. Compared with wild-type mice, 10-17 month old APP/PS1 mice failed to acquire CTA to saccharin. Mice that only possessed one of the two mutations were able to acquire CTA to the saccharin. In 2-5 month old APP/PS1 mice acquisition of CTA was disrupted despite the lack of extensive plaque deposition. However, further analysis indicated a potential gender difference in both the CTA deficit and onset of plaque deposition with females showing greater conditioned aversion.     

Recall of a previously acquired conditioned taste aversion in rats following lesions of the area postrema

A conditioned taste aversion was produced by pairing a novel sucrose solution with either 3 mEq lithium chloride or with 100 rad gamma radiation in rats with the area postrema intact. Lesions of the area postrema were then made in half of the rats exposed to each treatment and in rats that were not treated with the unconditioned stimulus. When tested for a conditioned taste aversion, all treated rats showed a significant aversion to the sucrose solution compared to the untreated control rats. There were no significant differences between rats with area postrema lesions and those with the area postrema intact, indicating that the lesions had no effect on the recall of the previously acquired aversion. The results are interpreted as being consistent with the hypothesis that the role of the area postrema in taste aversion learning is to monitor blood and cerebrospinal fluid for potential toxins and to transmit that information to the central nervous system.     

Differential effects of electrical stimulation of amygdala, caudate-putamen or substantia nigra pars compacta on taste aversion and passive avoidance in rats

The effect of unilateral, low-intensity subseizure electrical stimulation of the basolateral nucleus of the amygdala (ABL), caudate-putamen (CD) or substantia nigra pars compacta (SNC) on the acquisition and retention of a conditioned taste aversion and a step-down passive avoidance response were compared in two separate experiments. In Experiment 1 electrical stimulation of the ABL while rats were drinking saccharin prior to poisoning with LiCl disrupted conditioned taste aversion. Stimulation of the CD or SNC had no disruptive effect on taste aversion. In contrast, stimulation at all 3 brain loci disrupted the retention of a passive avoidance response in Experiment 2. The implications of these data for the hypothesis of dual neural control systems for shock avoidance behavior and taste aversion, are discussed.