Taste Aversion In Rats Research Articles

Deoxynivalenol (vomitoxin)-induced conditioned taste aversions in rats are mediated by the chemosensitive area postrema

The present experiments used a conditioned aversion to a novel saccharin taste to assess the aversive effects of deoxynivalenol (vomitoxin) administration, and to examine the putative mediating role of the chemosensitive area postrema (AP). In experiment 1 adult male rats drank a novel 0.15% saccharin solution followed by injection of deoxynivalenol ( n = 7; 0.125 mg/kg, IP) or vehicle ( n = 7; propylene glycol, 0.5 mg/kg). In subsequent two-bottle preference tests the rats conditioned with deoxynivalenol displayed significantly ( p < 0.01) lower absolute and relative saccharin intake levels in comparison to control rats which exhibited a strong preference for saccharin solution. In experiment 2 adult male rats received area postrema ablations ( n = 6) or sham lesions ( n = 6). On two conditioning days all rats drank a novel 0.15% saccaharin solution followed by injections of deoxynivalenol (0.125 mg/kg, IP). In subsequent two-bottle preference tests the sham-lesioned rats displayed a significant ( p < 0.01) aversion to the saccharin stimulus, relative to the area postrema-ablated rats which exhibited a preference for the saccharin solution. Thus, systemic administration of deoxynivalenol, following a novel taste, induced conditioned taste aversions which were mediated by the area postrema.

Changes of amygdaloid neuronal responses after acquisition of conditioned taste aversion in rats

Changes of amygdaloid neuronal responses after acquisition of conditioned taste aversion in rats

Differential involvement of gustatory insular cortex and amygdala in the acquisition and retrieval of conditioned taste aversion in rats

Lesion studies of the role of the gustatory insular cortex (GC) and amygdala (Am) in conditioned taste aversion (CTA) are confounded by the irreversibility of the intervention. Functional ablation methods allow more specific influencing of different phases of CTA acquisition and retrieval. Bilateral tetrodotoxin (TTX) blockade of GC (10 ng) or Am (3 ng) before or after saccharin drinking in rats with chronically implanted intracerebral cannulae showed that GC is indispensable for the initial processing of the taste stimulus but not for the association of the gustatory trace with the symptoms of LiCl poisoning. Gustatory signals can by-pass the blocked Am, the inactivation of which, however, impairs the gustatory trace-poisoning association. TTX injection into both GC and Am impairs CTA retrieval more than isolated blockade of either of these structures. It is argued that GC and Am implement processing of gustatory and visceral signals, respectively, but that formation and consolidation of the CTA engram proceeds outside forebrain, probably at the level of the brainstem.

Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats.

This report updates the bidirectional selective breeding of taste aversion (TA) prone (TAP) and TA resistant (TAR) rat lines from the 8th through the 22nd generations. A palatable saccharin solution and the aversive consequences of a cyclophosphamide injection are the respective conditioned stimulus (CS) and unconditioned stimulus (US) of line development. Nonsibling matings within each of the two extremes of TA conditionability have produced TAP and TAR lines having markedly different TA propensities. As previously reported, the substitution of a rotational (i.e., motion sickness) US for cyclophosphamide during TA conditioning also produced characteristic line differences in conditioned taste aversion acquisition. The present report extends the effective line separating USs to include injections of lithium chloride, emetine hydrochloride, and EtOH. A range of EtOH dose levels produced dose-dependent TAs within TAP rats but failed to induce TAs in TAR rats. Following the conclusion of TA testing, the administration of a hypnotic EtOH dose produced equivalent loss of righting capability and equivalent hypothermia in both TAP and TAR rats. The line differences in EtOH induced TA conditionability therefore do not reflect general line differences in EtOH sensitivity. The lines may be useful within studies of biological bases of TA conditionability and animal analog studies of prevention and treatment of alcohol dependence.

Relationship between vomiting and taste aversion learning in the ferret: studies with ionizing radiation, lithium chloride, and amphetamine

The relationship between emesis and taste aversion learning was studied in ferrets (Mustela putorius furo) following exposure to ionizing radiation (50-200 cGy) or injection of lithium chloride (1.5-3.0 mEq/kg, ip). When 10% sucrose or 0.1% saccharin was used as the conditioned stimulus, neither unconditioned stimulus produced a taste aversion, even when vomiting was produced by the stimulus (Experiments 1 and 2). When a canned cat food was used as the conditioned stimulus, lithium chloride, but not ionizing radiation, produced a taste aversion (Experiment 3). Lithium chloride was effective in producing a conditioned taste aversion when administration of the toxin was delayed by up to 90 min following the ingestion of the canned cat food, indicating that the ferrets are capable of showing long-delay learning (Experiment 4). Experiment 5 examined the capacity of amphetamine, which is a qualitatively different stimulus than lithium chloride or ionizing radiation, to produce taste aversion learning in rats and cats as well as in ferrets. Injection of amphetamine (3 mg/kg, ip) produced a taste aversion in rats and cats but not in ferrets which required a higher dose (> 5 mg/kg). The results of these experiments are interpreted as indicating that, at least for the ferret, there is no necessary relationship between toxin-induced illness and the acquisition of a CTA and that gastrointestinal distress is not a sufficient condition for CTA learning.

Acquisition of conditioned taste aversion in rats is mediated by ipsilateral interaction of cortical and mesencephalic mechanisms

The possibility to lateralize the neural circuits mediating conditioned taste aversion (CTA) has been examined by combination of functional hemidecortication and unilateral tetrodotoxin (TTX) injection into the parabrachial nucleus (PBN). Rats drinking saccharin (CS) during cortical spreading depression (CSD) in the right hemisphere and receiving unilateral PBN injection of TTX (3 ng) shortly before i.p. injection of lithium chloride (LiCl) (US) formed CTA when CSD and TTX were applied to the same hemisphere but not when applied to different hemispheres. Rats drinking saccharin with intact brain and receiving unilateral TTX overlapping with LiCl administration learned a weak CTA, the retrieval of which was disrupted by either ipsilateral or contralateral CSD during retention testing. It is concluded that CTA acquisition requires cooperation of ipsilateral cortical and subcortical centers but that formation of unilateral subcortical CTA engram does not warrant lateralization of the retrieval process.

HPLC-purified human satietin does not produce conditioned taste aversion in rats

Human satietin is thought to be an endogenous glycoprotein that can suppress food intake and body weight. However, it was also found to be aversive when rats infused intracerebroventricularly (ICV) with human satietin were subjected to a two-bottle taste aversion test. More recently, the human satietin previously thought homogenous was separated by HPLC into two Peaks, denoted as A and B. In the present study, male Sprague-Dawley rats were fitted with chronic third ventricle cannulas and presented with fluid for 1 h/day, while food was given ad lib. After training, the rats were ICV infused with either artificial cerebrospinal fluid, Peak A or Peak B of human satieton. Peak B significantly reduced short-term and 24-h food intake, whereas their fluid intake was nonsignificantly attenuated. Peak A had no affect on either food or fluid intake on the day it was administered. When the rats were given the two-bottle taste aversion test neither compound was found to be aversive. These data suggest that Peak B may contain satietin(s) which could be a candidate for an endogenous satiety agent.

Acquisition of conditioned taste aversion in rats is prevented by tetrodotoxin blockade of a small midbrain region centered around the parabrachial nuclei

A remarkable feature of conditioned taste aversion (CTA) is the resistance of the association between the gustatory trace and symptoms of poisoning against disruptive procedures. In an attempt to identify the neural substrate of this phase of CTA acquisition, thirsty rats were offered 0.1% saccharin for 15 min, were immediately afterwards anesthetized with pentobarbital, received stereotaxic injections of tetrodotoxin (TTX, 10 ng/μl) into various brainstem regions and were poisoned with IP injection of LiCl (0.15 M, 2% body weight). In Experiment 1, TTX prevented CTA acquisition when injected into the parabrachial nuclei but was ineffective in the lower medulla. TTX alone did not elicit CTA even at brain sites in which it caused death in 30% of the animals. In Experiment 2, the brainstem was systematically explored by a grid of bilateral TTX injections. A spatial gradient of the CTA disruption pointed to the parabrachial nuclei as the brain region responsible for the amnesic effect observed. Experiment 3 showed that a single TTX injection into the parabrachial nucleus on one side did not prevent CTA acquisition and that similarly ineffective were TTX injections in the sagittal plane both at the mesencephalic and bulbar levels. It is concluded that the pivotal role of the parabrachial nuclei in the formation of the permanent CTA engram can only be revealed by functional blockade which is more radical than that achieved during general anesthesia.

Characterization of a dose—response curve for nicotine-induced conditioned taste aversion in rats: Relationship to elevation of plasma β-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.

Deficits in conditioned heart rate and taste aversion in area postrema-lesioned rats

Previous studies have shown that area postrema (AP) lesions cause deficits in conditioned taste aversion in the rat. They also lead to chronically lowered heart rate which can be reversed by the animals' increased appetite for and ingestion of hypertonic saline. Although not previously examined in conditioned taste aversion, changes in autonomic nervous system activity as reflected in heart rate may be an important aspect of conditioning. The present study investigated the effects of AP lesions on heart rate conditioned responses (CRs) and unconditioned responses (UCRs). Two groups of AP lesioned and sham-operated rats, one that did and one that did not drink saline solution to raise heart rate, were studied. Both LiCl and scopolamine, which have opposite effects on heart rate, were the unconditioned stimulus (UCS) agents in two separate studies. In intact rats, LiCl-mediated conditioned taste aversion was associated with decreased conditioned stimulus (CS) intake and decreased heart rate Both effects were blunted by AP lesions, although all rats displayed heart rate UCRs to LiCl. The AP rats that drank saline behaved like intact rats exhibiting both a conditioned taste aversion and conditioned heart rate responses to the CS. Although CS intake decreased, no heart rate CRs developed with scopolamine. Scopolamine-mediated conditioned taste aversion was attenuated in both saline and non-saline drinking AP-lesioned groups. Thus, when conditioned taste aversion was associated with heart rate CRs, the AP lesion-induced deficit was counteracted by saline ingestion. Conversely, when there were no heart rate CRs, conditioned taste aversion was disrupted by the lesion regardless of saline ingestion.

Gamma radiation-induced conditioned taste aversions in rats: A comparison of the protective effects of area postrema lesions with differing doses of radiation

Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days ( p<0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable ( p>0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy.

Interleukin-1 induces conditioned taste aversion in rats: a possible explanation for its pituitary-adrenal stimulating activity

To investigate the possible aversive stimulus properties of peripherally administered interleukin 1 (IL-1), rats received two pairings of ingestion of a saccharin solution with various doses of recombinant rat interleukin 1 in a conditioned taste aversion paradigm, using 20 mg/kg lipopolysaccharide endotoxin as a positive control. Rats treated with 1 and 10 μg IL-1 showed a dose-dependent reduced preference for saccharin together with dose-dependent impairments in weight gain. Since these effects were obtained within the range of doses that has been previously reported to stimulate the release of ACTH, it is proposed that this last action of IL-1 is likely to be secondary to the aversive effects of IL-1.

Age-related differences in the US preexposure effect on conditioned taste aversion in rats

Weanling, young adult, and old Wistar albino rats were used to determine whether the unconditioned stimulus (US) preexposure effect on conditioned taste aversion is age-related. The rats at each age level were given five preconditioning injections of either.15 M lithium chloride or physiological saline. These groups were then subdivided and given either conditioning or control treatments. Conditioning consisted of 10 min access to a saccharin solution followed 20 min later by an injection of.15 M lithium chloride. The control treatment consisted of 10 min access to saccharin followed 20 min later by a saline injection. Twenty-four hours later the animals were given a 24-h two-bottle (saccharin vs. water) test. Results indicated that as age increased the US preexposure was less effective in attenuating conditioned taste aversion. These results were interpreted in terms of age differences in response to the conditioning context.

Characterization of central nicotinic receptors by studies on the nicotine cue and conditioned taste aversion in rats

Some recent studies on the discriminative stimulus (cue) and conditioned taste aversion (CTA) effects of nicotine are reviewed. The characteristics of the nicotine cue correlate well with those of high affinity nicotine binding in studies comparing different nicotinic agonists. The dose of nicotine used for training a discrimination is an important variable determining patterns of generalization. The effects of antagonists on the nicotine cue are also compatible with ligand-binding studies although the lack of competitive antagonists generates unsolved problems for investigators. The CTA produced by nicotine has pharmacological characteristics like the nicotine cue. Both effects are produced at CNS sites that resemble to a certain extent the cholinoceptive sites in autonomic ganglia. The small differences in the degree of stereoselectivity of the two effects or in their sensitivity to antagonists do not constitute substantive evidence for mediation by different receptors. The major differences between the procedures lies in their general psychopharmacological characteristics rather than in any special qualities of the response to nicotine. For example, the nicotine cue is not produced by agents from other pharmacological classes whereas a wide range of different drugs can produce CTA. The concept of multiple types of CNS nicotinic receptors, as supported by certain biochemical studies, requires further evaluation in behavioural systems.

Phenylethylamine-induced taste aversion in rats and mice

Phenylethylamine (PEA) has the same structure as amphetamine (AMP) except that PEA lacks a methyl group at the alpha carbon. Although these analogues produce many similar neurobehavioral actions, a previous study found that PEA did not support formation of conditioned taste aversion (CTA). Using somewhat different procedures, in the present study a transient taste aversion was seen in rats. Use of noradrenergic blocking agents to attempt to pharmacologically tailor PEA action to make it more like that of AMP did not improve efficacy to form CTA. A robust PEA-induced CTA was seen in mice even when PEA produced multiple seizures.

Induction of conditioned taste aversion in rats by GABA or other amino acids

GABA included in the diet is known to reduce food intake and growth of rats fed a low protein diet. Experiments were designed to determine if GABA or other small neutral amino acids would affect food intake if they were administered separately from the diet, and if such amino acids could induce a conditioned taste aversion (CTA) to saccharin. Intubated or injected GABA or α-aminoisobutyric acid (AIB), a non-metabolizable isomer of GABA, reduced food intake. When rats were fed a low protein diet, IP injection of threonine (2 mmoles/200 g rat) induced CTA but did not depress food intake; serine (3 mmoles/200 g rat) induced CTA and caused only a small reduction in food intake. Another isomer, α-amino-n-butyric acid did not affect food intake or induce CTA at the tested concentrations. Adaptation to a high protein diet, which increases enzymatic degradation of many amino acids including GABA and serine, lessened severity of GABA-induced CTA and eliminated that caused by serine. CTA to saccharin can be induced by certain amino acids; the mechanism is unknown but may involve malaise or other adverse sensations.

Stressors in the learned helplessness paradigm: Effects on body weight and conditioned taste aversion in rats

Changes in body weight and taste aversion in the learned helplessness paradigm were examined. In Experiment 1, adult male Sprague-Dawley rats drank saccharin or a control solution, followed by either 100 inescapable shocks or simple restraint. Rats were weighed daily and were tested for saccharin aversion two days after the stress session. Shocked rats gained less weight in the days after stress than restrained controls. Saccharin aversion was apparent only among rats that had consumed saccharin before the stress session. Experiment 2 examined whether control over shock affected body weight or taste aversion. Home-cage controls were included to assess the effects of restraint alone. In addition, the combined effects of shock and a toxin on aversion were studied. Rats drank saccharin solution, followed by escapable or inescapable shock, restraint, or no treatment. Then half of each group was injected with saline; the other half was injected with lithium chloride. As in Experiment 1, shock reduced body weight relative to restraint or no treatment, and shock produced a taste aversion among saline-treated rats. However, shock attenuated the aversion produced by lithium chloride, as did simple restraint. There were no differences in body weight or taste aversion between escapably and inescapably shocked rats. These results suggest a role for stress in the anorexia and weight loss associated with clinical depression and may have implications for theories of learning and learned helplessness.

Conditioned taste aversion in rats subjected to anaphylactic shock.

Conditioned taste aversion in rats subjected to anaphylactic shock.

Buspirone antagonizes the expression of conditioned taste aversion in rats

AbstractWhen the parameters of taste aversion conditioning and testing have been appropriately adjusted, benzodiazepines and barbiturates will markedly antagonize the expression of moderate taste aversions in rats. We call this the taste aversion conflict model of anxiety. In the present study, we investigate whether buspirone HCl (buspirone; p.o. and i.p.) is active in the taste aversion conflict model and whether buspirone will also increase unsuppressed saccharin (SACC) intake. We also investigated the effects of imipramine, desipramine, phenelzine sulfate, chlorpromazine, scopolamine and d‐amphetamine sulfate in the taste aversion conflict model. To assess the possible effects of buspirone on the GABA‐benzodiazepine supramolecular receptor complex, we compared buspirone with certain benzodiazepines, meprobamate and sodium phenobarbital on the antagonism of pentylenetetrazol‐induced lethality in mice. Unlike benzodiazepines, meprobamate and phenobarbital, buspirone did not antagonize pentylenetetrazol‐induced lethality. However, like those other anxiolytics, buspirone markedly antagonized the expression of conditioned taste aversion. All nonanxiolytic drugs tested had either no effect or very slight effects on the expression of conditioned taste aversion. These results suggest that the taste aversion conflict model is sensitive to novel anxiolytics and that it is selective for drugs clinically effective in the treatment of generalized anxiety disorders in man.

Exposure to magnetic resonance imaging does not produce taste aversion in rats

A taste aversion test was used to evaluate possible toxic effects of magnetic resonance imaging (MRI). Thirty male Sprague-Dawley rats were randomly assigned to four groups: Group One (n=10) received 30 minutes exposure inside the MRI scanner; Group Two (n=10) received a sham exposure to the MRI scanner; Group Three (n=5) was injected with 0.15 M lithium chloride; and Group Four (n=5) was injected with vehicle. All groups were given 10 minutes access to a 0.1% saccharin solution immediately prior to their respective treatment. The rats treated with lithium chloride displayed a taste aversion to the saccharin solution upon subsequent testing over an eight day period. The two control groups (Two and Four) and the rats exposed to MRI did not display any aversion to the saccharin solution. These results are compared to other studies that have shown that magnetic fields can influence biological systems.