Conditioned taste aversion induced by wheel running: further evidence on wheel running duration

Rats given access to a running wheel after drinking a flavored solution subsequently drink less of that liquid. It has been suggested that suppression of intake is the result of conditioned taste aversion (CTA). This study explored whether the magnitude of CTA is related to time in the wheel (i.e., amount of wheel running). During 4 days of conditioning, rats drank an orange liquid for 60 min. Immediately after drinking, experimental rats were transferred to running wheels for either 20 or 60 min. Control animals remained in their home cages. Following the conditioning phase, all rats received a preference test composed of the paired flavored liquid (i.e., orange solution) and water. Rats in both experimental groups (20 and 60 min) decreased their consumption of the orange flavored liquid, but no difference in CTA was found between these groups. Wheel running, whether for 20 or 60 min, suppresses the consumption of a liquid consumed immediately before wheel access. These findings are discussed in terms of discrepancies between CTA induced by wheel running and CTA induced by emetic agents.     

Dissociation of conditioned taste avoidance from conditioned disgust reactions induced by wheel running in rats

It is well established that wheel running in rats produces conditioned taste avoidance; that is, rats that run in wheels after consuming a novel-tasting solution later consume less of that solution than rats that do not run. In experiment 1, we found that wheel running also produces conditioned disgust reactions, indicated by gapes elicited by both the taste and context that were experienced before running. Experiment 2 showed that the conditioned disgust reactions were likely not due to running itself but to a by-product of running, the rocking of the wheel that occurs when the running stops. When rocking was reduced, the disgust reactions were also reduced, but consumption of the taste solution was not changed, showing dissociation of conditioned taste avoidance and disgust. These findings indicate that the taste avoidance induced by wheel running itself is more like the taste avoidance produced by rewarding drugs than that produced by nausea-inducing drugs.     

Forced and voluntary exercise counteract insulin resistance in rats: the role of coping style

There are large individual differences in the success rates of exercise intervention programs aimed at the prevention and treatment of obesity-related disorders. In the present study, we tested the hypothesis that differences in coping style may impact the success rates of these intervention programs. We tested insulin responses before and after voluntary wheel running in both passive (insulin resistant) Roman Low Avoidance (RLA) and proactive (insulin sensitive) Roman High Avoidance (RHA) rats using intravenous glucose tolerance tests (IVGTTs). To control for a potential difference between voluntary and forced exercise, we also included RLA and RHA rats that were subjected to forced running. We found the following: 1) when given the opportunity to run voluntarily in a running wheel, passive RLA rats run more than proactively than RHA rats; 2) voluntary exercise leads to a normalization of insulin responses during an IVGTTs in RLA rats; and 3) there were no behavioral and physiological differences in efficacy between voluntary and forced running. We conclude that exercise, both forced and voluntary, is a successful lifestyle intervention for the treatment of hyperinsulinemia, especially in individuals with a passive coping style.     

Forward conditioning with wheel running causes place aversion in rats

Backward pairings of a distinctive chamber as a conditioned stimulus and wheel running as an unconditioned stimulus (i.e., running-then-chamber) can produce a conditioned place preference in rats. The present study explored whether a forward conditioning procedure with these stimuli (i.e., chamber-then-running) would yield place preference or aversion. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, but confinement in the other was not. After four repetitions of this treatment (i.e., differential conditioning), a choice preference test was given in which the rat had free access to both chambers. This choice test showed that the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, a 60-min running opportunity after confinement in a distinctive chamber caused conditioned aversion to that chamber after four paired trials. This result was discussed with regard to the opponent-process theory of motivation.     

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。     

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.     

Timing of omitted events: an analysis of temporal control of inhibitory behavior

This paper reviews research designed to investigate the temporal control of inhibitory responding using rats as subjects. One area of investigation has focused on the role of temporal variables in conditioned inhibition produced using Pavlov's [Pavlov, I.P., 1927. Conditioned Reflexes. Oxford University Press, London, 430 pp.] procedure. These studies have found that evidence of conditioned inhibition obtained by negative summation testing is strongest when the conditioned inhibitor signals the omission of the unconditioned stimulus (US) at the same temporal location as a transfer excitor signals presentation of the US [e.g., Barnet, R.C., Miller, R.R., 1996. Temporal encoding as a determinant of inhibitory control. Learn. Motiv. 27, 73-91]. Similarly, retardation of acquisition of behavioral control by a previously inhibitory conditioned stimulus (CS) is maximal when the inhibitory CS is paired with the US at the same temporal location as the inhibitor had previously signaled US omission [Burger, D., Denniston, J.C., Miller, R.R., 2001. Temporal coding in condition inhibition: retardation tests. Anim. Learn. Behav. 29, 281-290]. Other lines of research designed to assess the associative structure of temporal control of inhibition [e.g., Denniston, J.C., Blaisdell, A.P., Miller, R.R., 2004. Temporal control in conditioned inhibition: analysis of associative structure of inhibition. J. Exp. Psychol. Anim. Behav. Process. 30, 190-202] are reviewed, as is the assessment of temporal control of inhibition produced through extinction [Denniston, J.C., Miller, R.R., 2003. The role of temporal variables in inhibition produced through extinction. Learn. Behav. 31, 35-48]. These collective observations are discussed in terms of the temporal coding hypothesis [Matzel, L.D., Held, F.P., Miller, R.R., 1988. Reexamination of simultaneous and backward conditioning: Implications for contiguity theory. Learn. Motiv. 19, 317-344].     

Effect of extra running on running-based taste aversion in rats

Voluntary running in an activity wheel endowed rats with aversion to a taste solution consumed before the running. This running-based taste aversion was attenuated by extra running opportunities interspersed among the taste–running pairings, but the attenuating effect was reduced by signaling the extra running by another taste cue. These results correspond to the so-called degraded contingency effect and cover-cue effect in the traditional preparations of Pavlovian conditioning.     

Tamoxifen produces conditioned taste avoidance in male rats: An analysis of microstructural licking patterns and taste reactivity

Estrogen receptor activation has been shown to reduce body weight and produce a conditioned reduction in food intake in male rats that is putatively mediated by estradiol's suggested aversive effects. Evidence has shown that the selective estrogen receptor modulator tamoxifen used in the prevention and treatment of breast cancer may also produce changes in food intake and body weight, which are known to impact cancer development and survival. The purpose of the present study was to examine whether tamoxifen produces a conditioned reduction in intake similar to estradiol by producing a conditioned aversion. A one bottle lickometer test was used to examine conditioned changes in sucrose drinking, while the taste reactivity test was used to measure rejection reactions, which serve to index aversion in rats. A backward conditioning procedure that consisted of 3 conditioning days and one vehicle test day was used to examine conditioned changes in 0.3 M sucrose intake and taste reactivity. Our results show that tamoxifen produced a conditioned reduction in sucrose drinking in a one bottle fluid intake test that was similar to the effects produced by estradiol (positive control); however, no active rejection reactions were produced by either tamoxifen (1 and 10 mg/kg) or estradiol. The present results suggest that tamoxifen, at the doses used in the present study, acts as an estrogen receptor agonist to regulate food intake and that the conditioned reduction in intake produced by tamoxifen and estradiol reflects conditioned taste avoidance rather than conditioned taste aversion.     

Taste aversion learning induced by delayed swimming activity

The experiment reported here demonstrated that forced swimming endows rats with aversion to a taste solution consumed 30 min before the swimming. The experimental rats were allowed to drink 0.2% sodium saccharin solution, which was followed by a 30-min empty interval, and then a 20-min swimming opportunity in water. Compared with the control rats, which were returned to their home cages after drinking the saccharin, the experimental rats drank a small amount of saccharin solution both in the later sessions of one-bottle training and in the subsequent two-bottle choice (saccharin versus tap water) testing. The delayed swimming procedure was as effective as an immediate swimming procedure, extending the generality of the swimming-induced taste aversion, which we recently discovered with the immediate swimming procedure.     

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.     

Effects of post-treatment retention interval and context on neophobia and conditioned taste aversion

We have repeatedly observed that a delay between acquisition and test, and the nature of the context in which the delay is spent, modulates latent inhibition (LI) of conditioned taste aversion (CTA; e.g. [Anim. Learn. Behav. 28 (2000) 389; Anim. Learn. Behav. 30 (2002) 112]). The present paper analysed the effects of delayed testing and treatment context after flavor exposure on the recovery of neophobia (Experiment 1) and on extinction after simple conditioning (Experiment 2). Two experiments were conducted with the same factorial design (2x2: 1 day versus 21 days of delay between first and second stage, and home versus experimental cages as place of experimental treatment). There were independent effects of both variables on habituation of neophobia and conditioning strength as measured on extinction trials. The long delay produced a reduction of neophobia (Experiment 1) and an increase in conditioning (Experiment 2). In addition, more of the flavored solution was consumed when the experimental treatment was conducted in the home cage than in the experimental cage (Experiment 1), and there was stronger conditioning when the delay period took place in the experimental cages than in the home cages (Experiment 2). The implications of these results for LI, as well as their relevance for experiments that use the CTA paradigm, are discussed.     

Formation of taste aversions in the rat

The presence of correlation between the initial attitude of animals to a certain taste agent and the intensity of conditioned taste aversion (CTA) after LiCl poisoning was studied in nonlineal male white rats. 4 types of behavioural reactions were revealed: 1) the nonspecific inhibitory reaction to the situation in which CTA was elaborated; 2) specific associative-adaptive connection of CTA with the taste agent used (0,1% saccharine solution); 3) complex reaction consisting of the two first ones; 4) the same drinking behaviour as that before CTA elaboration. Moreover, a correlation was found between the initial attitude of animals to certain taste agent and the intensity of CTA after pairing of this agent with subsequent poisoning.     

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.     

Blockade of ethanol induced conditioned taste aversion by 3-amino-1,2,4-triazole: evidence for catalase mediated synthesis of acetaldehyde in rat brain

This investigation seeks to present evidence for the oxidation of ethanol in the brain via the peroxidatic activity of catalase and simultaneously provide evidence for the role of central acetaldehyde (ACH) in the mediation of an ethanol-induced conditioned taste aversion (CTA). Ethanol is capable of inducing a conditioned taste aversion. Pretreatment with the catalase inhibitor, 3-amino-1,2,4-triazole (AT), shows an attenuation of this ethanol-induced CTA. Animals receiving ethanol injections showed a CTA to a novel solution paired with a drug administration, while ethanol injected animals pretreated with AT did not show a CTA to ethanol administration. This effect of AT appears to be specific to the effects of ethanol as CTA's to morphine and lithium chloride were not affected by AT pretreatment. Peripheral levels of ethanol were the same in all animals regardless of pretreatment indicating that AT had no effect on peripheral levels of ethanol. These data increase support for the notion that acetaldehyde is produced directly in the brain and that it may be the agent mediating some of the psychopharmacological properties of ethanol.     

Overshadowing of running-based taste aversion learning by another taste cue

Training rats with serial presentations of two taste solutions before confinement in an activity wheel (X → A → running) resulted in weak aversion to taste X, compared to a training procedure without the presentation of A. Demonstration of the overshadowing effect in the present study provides another parallel feature between running-based taste aversion learning and Pavlovian conditioning preparations including poison-based taste aversion learning. It also indirectly supports the claim that cue competition causes degraded contingency effect and cover-cue effect in rats’ running-based taste aversion (Nakajima, 2008).     

Gamma-L-glutamyl-taurine (Litoralon) affects conditioned taste aversion in rats

The dipeptide gamma-L-glutamyl-taurine (Litoralon) reduced neophobia of rats at a dose of 5.0 mg/kg (i.p.) in a "one-bottle forced choice paradigm" for conditioned taste aversion (CTA), but did not significantly affect the rats' "memory" of intoxication following chronic treatment at doses of 0.05, 0.50 and 5.00 mg/kg (i.p.). Acute treatment with Litoralon (10-1000 micrograms/kg, i.p.) did not affect CTA checked in a "two-bottle test", when administered immediately following the unconditioned stimulus (LiCl injection). In contrast, when given 90 min prior to the retention test, the injection of Litoralon (50.0 micrograms/kg) and gamma-aminobutyryl ethanolamine phosphate (100 and 500 micrograms/kg) resulted in a significantly higher intake of saccharin solution by the rats. This effect is comparable to the action of diazepam tested in the same experimental procedure. The results support our hypothesis about the anti-conflict potencies of these dipeptides, exerted by reducing aversion of phobia and/or the anxiety level of the animals in the experimental situation.     

Acute 3rd-ventricular amylin infusion potently reduces food intake but does not produce aversive consequences

In this study, a conditioned taste aversion (CTA) paradigm was used to assess the possibility that 3rd-ventricular (i3vt) administration of the pancreatic hormone amylin produces aversive consequences that secondarily reduce food intake independently of the normal regulation of energy balance. After 1-h daily access to water for 7 days, rats were given 1-h access to a 0.15% saccharin solution, followed immediately by i3vt amylin (100 pmol) in one group (n=7) and i3vt CSF vehicle in another (n=7). As positive control for the formation of a CTA, a third group of seven rats received intraperitonial (i.p.) lithium chloride (LiCl). Saline was given i.p. to a fourth group (n=7) as control for i.p. LiCl. As expected, the LiCl rats exhibited a marked aversion to the saccharin in a subsequent two-bottle intake test. In contrast, although the 100 pmol i3vt amylin dose is substantially higher than that required to reduce food intake, no evidence of a CTA was observed in the rats that had received i3vt amylin. In summary, these data are consistent with the conclusion that acute i3vt amylin infusion does not reduce food intake by producing aversive consequences.     

Oxytocin levels in the posterior pituitary and in the heart are modified by voluntary wheel running

We hypothesized that voluntary wheel running results in increased secretion of oxytocin, a peptide involved in the stress response. An additional hypothesis was that prolonged exercise affects oxytocin levels in the heart, which is in line with the potential role of oxytocin in cardiovascular functions. Voluntary wheel running lasted 3 weeks and daily running distances increased progressively reaching maximum levels about 8 km (Sprague-Dawley rats) and 4 km (Lewis strain). The exercise resulted in significant reduction of epididymal fat, slight increase in glucose transporter GLUT4 mRNA levels and significant enhancement of plasma density. Voluntary exercise failed to influence plasma oxytocin levels either in Lewis or Sprague-Dawley rats, but it resulted in a significant decrease of oxytocin concentrations in the posterior pituitary. Plasma oxytocin concentrations were not modified even if the measurements were made in the dark phase of the day. In voluntary wheel running Sprague-Dawley rats, the content of oxytocin in the right heart atrium was lower than in controls. Thus, the present findings demonstrate that prolonged voluntary wheel running results in a decrease in pituitary oxytocin content without evident changes in hormone concentrations in peripheral blood. However, prolonged exercise used has a significant impact on oxytocin levels in the heart.     

Behavioral discrimination between glutamate and the four basic taste substances in mice

1. Behavioural studies using the conditioned taste aversion (CTA) paradigm in mice showed that aversion conditioned to monosodium L-glutamate (MSG), which elicits a unique taste in humans, did not strongly generalize to any of the four basic taste stimuli, suggesting that mice could behaviourally discriminate between MSG and the four basic taste stimuli. 2. Denervation of bilateral glossopharyngeal nerve significantly increased behavioural similarities (the strength of generalization in the CTA paradigm) between MSG and sodium salts. This was not the case after destruction of the bilateral chorda tympani nerve. 3. These results suggest that taste information of glossopharyngeal nerve plays a more important role in the behavioural discrimination between MSG and the four basic tastes than does that of the chorda tympani nerve.