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.     

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.     

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.     

Blocking of conditioned taste avoidance induced by wheel running

In Experiment 1, compared to non-reinforced presentation of a food stimulus (A → no US), the association of a food stimulus with wheel running (A → US) blocked subsequent avoidance of a distinctive flavor (X), when both the food and flavor were followed by wheel running (AX → US). Experiment 2 replicated and extended the blocking effect, demonstrating that the amount of avoidance of X after AX → wheel training depended on the correlation between A-alone trials and wheel running—the predictiveness of the A stimulus. The present study is the first to demonstrate associative blocking of conditioned taste avoidance (CTA) induced by wheel running and strongly implicates associative learning as the basis for this kind of avoidance.     

Conditioned taste avoidance induced by forced and voluntary wheel running in rats

Voluntary exercise by rats running in a freely rotating wheel (free wheel) produces conditioned taste avoidance (CTA) of a flavored solution consumed before running [e.g., Lett, B.T., Grant, V.L., 1996. Wheel running induces conditioned taste aversion in rats trained while hungry and thirsty. Physiol. Behav. 59, 699-702]. Forced exercise, swimming or running, also produces CTA in rats [e.g., Masaki, T., Nakajima, S., 2006. Taste aversion induced by forced swimming, voluntary running, forced running, and lithium chloride injection treatments. Physiol. Behav. 88, 411-416]. Energy expenditure may be the critical factor in producing such CTA. If so, forced running in a motorized running wheel should produce CTA equivalent to that produced by a similar amount of voluntary running. In two experiments, we compared forced running in a motorized wheel with voluntary running in a free wheel. Mean distance run over 30 min was equated as closely as possible in the two apparatuses. Both types of exercise produced CTA relative to sedentary, locked-wheel controls. However, voluntary running produced greater CTA than forced running. We consider differences between running in the free and motorized wheels that may account for the differences in strength of CTA.     

Taste aversion and frugivore preference

Summary I tested the hypothesis that thrushes avoid certain species of fruits because of their taste. It was found that thrushes had significant preferences and aversions for the flavours of certain species of fruit. Several species of fruit which thrushes avoided contained identified toxins. It is speculated that some species of plants have evolved fruit toxins to prevent thrushes from consuming fruits and dispersing seeds to unfavourable habitats.     

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.     

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.     

Effect of short-term prefeeding and body weight on wheel running and responding reinforced by the opportunity to run in a wheel

A biobehavioural analysis of activity anorexia suggests that the motivation for physical activity is regulated by food supply and body weight. In the present experiment, food allocation was varied within subjects by prefeeding food-deprived rats 0, 5, 10 and 15 g of food before sessions of lever pressing for wheel-running reinforcement. The experiment assessed the effects of prefeeding on rates of wheel running, lever pressing, and postreinforcement pausing. Results showed that prefeeding animals 5 g of food had no effect. Prefeeding 10 g of food reduced lever pressing for wheel running and rates of wheel running without a significant change in body weight; the effect was, however, transitory. Prefeeding 15 g of food increased the animals' body weights, resulting in a sustained decrease of wheel running and lever pressing, and an increase in postreinforcement pausing. Overall the results indicate that the motivation for physical activity is regulated by changes in local food supply, but is sustained only when there is a concomitant change in body weight.     

Taste aversion involving central opioid antagonism is potentiated in morphine-dependent rats

A sensitive taste conditioning test was used to measure the aversive effect of a single intraventricular (i.c.v.) or subcutaneous (s.c) injection of an opioid antagonist that readily crosses the blood brain barrier (naltrexone), and one of two that do not (methylnaltrexone and diallylnormorphinium). This was done in drug-naive rats and in rats implanted 5 days earlier with a pellet containing 75 mg morphine. It was found that the morphine exposure had no significant effect on the dose-response curve of the taste aversion produced by s.c. methylnaltrexone and s.c. diallynormorphinium but reduced the lowest effective dose for the other antagonist treatments from three to more than 100 times. Consideration of the data, together with the pharmacokinetic properties of the drugs and the routes of administration used, supported a conclusion that only those aversions involving central antagonist activity show the potentiation effect of chronic morphine treatment. The findings were also discussed with regard to the location of receptors important for aversions produced by opioid antagonists in naive rats.     

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.     

Progesterone stimulates running wheel activity in adrenalectomized-ovariectomized rats.

Daily treatment with progesterone (5 mg) increased running wheel activity, food intake, and body weight of adrenalectomized-ovariectomized rats. These effects of progesterone are quite similar to those of various corticosteroid treatments in adrenalectomized rats reported previously. In addition, the activity-stimulating action of progesterone is just the opposite of its effect in intact and estradiol-primed ovariectomized rats. These observations are consistent with the hypothesis that the principal role of progesterone in the regulation of body weight is to antagonize the actions of estradiol and that the actions of excessive doses of progesterone in adrenalectomized-ovariectomized rats are simply a by-product of its corticosteroidlike, health-promoting properties.     

Bivalent effects of wheel running on taste conditioning

We replicated the finding of bivalent conditioning of tastes by wheel running by Hughes and Boakes (2008), but without pre-exposure to the wheel. Rats received six days of conditioning with a flavoured solution presented for 10 min before a 40-min placement in a running wheel and another flavoured solution presented for 10 min after. A highly palatable liquid meal replacement was used as a vehicle for the flavours to encourage consumption, allowing us to equate before and after presentation intervals. Relative to a third flavour, we found that the taste preceding wheel running was consumed less, and the taste that followed wheel running was consumed more. Novel wheel running can therefore condition both taste avoidance and taste preference.     

Intracerebroventricular injection of ghrelin decreases wheel running activity in rats

There is an increasing interest in elucidating the molecular mechanisms by which voluntary exercise is regulated. In this study, we examined how the central nervous system regulates exercise. We used SPORTS rats, which were established in our laboratory as a highly voluntary murine exercise model. SPORTS rats showed lower levels of serum ghrelin compared with those of the parental line of Wistar rats. Intracerebroventricular and intraperitoneal injection of ghrelin decreased wheel-running activity in SPORTS rats. In addition, daily injection of the ghrelin inhibitor JMV3002 into the lateral ventricles of Wistar rats increased wheel-running activity. Co-administration of obestatin inhibited ghrelin-induced increases in food intake but did not inhibit ghrelin-induced suppression of voluntary exercise in rats. Growth hormone secretagogue receptor (GHSR) in the hypothalamus and hippocampus of SPORTS rats was not difference that in control rats. We created an arcuate nucleus destruction model by administering monosodium glutamate (MSG) to neonatal SPORTS rats. Injection of ghrelin into MSG-treated rats decreased voluntary exercise but did not increase food intake, suggesting that wheel-running activity is not controlled by the arcuate nucleus neurons that regulate feeding. These results provide new insights into the mechanism by which ghrelin regulates voluntary activity independent of arcuate nucleus neurons.     

Changes in running mechanics and spring-mass behavior induced by a mountain ultra-marathon race

Changes in running mechanics and spring-mass behavior due to fatigue induced by a mountain ultra-marathon race (MUM, 166km, total positive and negative elevation of 9500m) were studied in 18 ultra-marathon runners. Mechanical measurements were undertaken pre- and 3h post-MUM at 12km h(-1) on a 7m long pressure walkway: contact (t(c)), aerial (t(a)) times, step frequency (f), and running velocity (v) were sampled and averaged over 5-8 steps. From these variables, spring-mass parameters of peak vertical ground reaction force (F(max)), vertical downward displacement of the center of mass (Δz), leg length change (ΔL), vertical (k(vert)) and leg (k(leg)) stiffness were computed. After the MUM, there was a significant increase in f (5.9±5.5%; P<0.001) associated with reduced t(a) (-18.5±17.4%; P<0.001) with no change in t(c), and a significant decrease in both Δz and F(max) (-11.6±10.5 and -6.3±7.3%, respectively; P<0.001). k(vert) increased by 5.6±11.7% (P=0.053), and k(leg) remained unchanged. These results show that 3h post-MUM, subjects ran with a reduced vertical oscillation of their spring-mass system. This is consistent with (i) previous studies concerning muscular structure/function impairment in running and (ii) the hypothesis that these changes in the running pattern could be associated with lower overall impact (especially during the braking phase) supported by the locomotor system at each step, potentially leading to reduced pain during running.     

Taste aversion learning and aging: a comparison with the effect of dorsal hippocampal lesions in rats

The relationship between hippocampal function and aging was explored in Wistar rats using taste aversion learning by comparing the performance of adult dorsal hippocampal lesioned and fifteen-month-old intact rats with that of adult intact rats. In experiment 1 the conditioned blocking phenomenon was absent in the hippocampal and the aging rats. Unlike the adult intact rats, the hippocampal and aging rats were not impaired in acquiring a learned aversion to a cider vinegar solution (3 %) presented as a serial compound with a previously conditioned saccharin solution (0.1 %). In experiment 2 both the hippocampal and the aging rats developed reduced aversions to a saline solution (0.5 %) followed by an i.p. injection of lithium chloride (0.15 M; 2 % b.w.) if the taste solution was previously preexposed without consequences. This latent inhibition effect was similar to that seen in intact adult rats. In both experiments, the aging rats exhibited enhanced conventional learned taste aversions. It is concluded that aging is not a unitary process but induces both hippocampal dependent and hippocampal independent complex changes in the functioning of the neural circuits, implementing taste aversion learning.     

Role of IL-4 in aversion induced by food allergy in mice

To ascertain the role of IL-4 in aversion to antigen induced by food allergy, wild type and IL-4 deficient BALB/c mice were sensitized with ovalbumin and challenged orally with egg white. Sensitized wild type mice had increased production of IL-4 by spleen and mesenteric lymph node cells in vitro, higher levels of serum anti-ovalbumin IgE and IgG1, aversion to ingestion of the antigen and loss of body weight after continuous oral challenge. Intestinal changes in wild type sensitized mice included eosinophil infiltration and increased mucus production. The IL-4 deficiency impaired the development of food allergy and the aversion to antigen, suggesting the involvement of the antigen specific antibodies. When IL-4 deficient mice received serum from sensitized wild type donors, the aversion was restored. These results indicate that production of IL-4 and specific IgE/IgG1 antibodies correlate with aversion to antigen induced by food allergy in mice.