Forward conditioning with wheel running causes place aversion in rats

Forward conditioning with wheel running causes place aversion in rats

Behavioural Processes 79 (2008) 43–47 Contents lists available at ScienceDirect Behavioural Processes journal homepage:

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Behavioural Processes 79 (2008) 43–47

Contents lists available at ScienceDirect

Behavioural Processes journal homepage:

Forward conditioning with wheel running causes place aversion in rats Takahisa Masaki, Sadahiko Nakajima ∗ Psychology Section, Department of Integrated Psychological Science, Kwansei Gakuin University, Nishinomiya, Hyogo 662-8501, Japan

a r t i c l e

i n f o

Article history: Received 12 February 2008 Received in revised form 8 April 2008 Accepted 23 April 2008 Keywords: Conditioned place aversion Place conditioning Activity wheel Running Exercise Rat

a b s t r a c t 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-thenrunning) 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. © 2008 Elsevier B.V. All rights reserved.

1. Introduction Lett and Grant (1996) discovered that running in an activity wheel endowed laboratory rats with aversion to a taste substance consumed prior to running. A number of studies have successfully replicated the running-based taste aversion using different rat strains, taste stimuli, lengths of the running opportunity, numbers of taste–running trials, and deprivation conditions (see Boakes and Nakajima, in press, for a review). Because a correlation of a target taste and wheel running is necessary for establishing the taste aversion, the running-based taste aversion has been discussed in the framework of Pavlovian conditioning. Namely, the taste serves as the conditioned stimulus (CS) and running as the aversive unconditioned stimulus (US). Despite its aversive US nature when paired with a taste CS, wheel running has a positive reinforcing property for instrumental responses such as lever-pressing (e.g., Kagan and Berkun, 1954; Collier and Hirsch, 1971; Iversen, 1993; Belke, 1996, 1997) and Tmaze learning (Livesey et al., 1972). Lett et al. (2000, 2001a, 2002) found that wheel running also works as a rewarding US for establishing a conditioned place preference (see also Belke and Wagner, 2005, for a demonstration of instrumental reinforcement and conditioned place preference in the same rats). In their experiments, rats were first given an opportunity to run in an activity wheel and then confined in a distinctive chamber. On other days the rats were

∗ Corresponding author. Fax: +81 798 54 6076. E-mail address: [email protected] (S. Nakajima). 0376-6357/$ – see front matter © 2008 Elsevier B.V. All rights reserved. doi:10.1016/j.beproc.2008.04.006

confined in the other chamber without running. The subsequent choice test showed that the rats spent more time in the runningpaired chamber than in the unpaired chamber. Assuming that the target chamber functioned as a CS and the wheel running as a US, their finding implies that backward pairings of these stimuli endow the rats with conditioned preference for the target chamber. Lett et al. (2001b) also reported that a taste–running–chamber sequence simultaneously establishes taste aversion and place preference in the rats. An account for the ambivalent nature of wheel running shown in the studies on running-based taste aversion and place preference is in terms of selective associations. Namely, aversive and rewarding properties of running are selectively associated with taste and chamber cues, respectively (see Sherman et al., 1980, for a similar explanation for morphine-based taste aversion and place preference). However, it seems premature to conclude from the available studies on running-based place preference (Belke and Wagner, 2005; Lett et al., 2000, 2001a,b, 2002) that wheel running always works as a rewarding US when paired with a chamber, because they employed backward conditioning procedures and repeated pairing of a CS and a US in a backward fashion (i.e., US–CS pairing) sometimes causes conditioning of a process which is opposite of the process primarily elicited by the US (Schull, 1979; Solomon, 1980; Wagner, 1981; Wagner and Larew, 1985). Indeed, the backward conditioning procedure is one of the ways to yield inhibitory conditioning (see LoLordo and Fairless, 1985; Hall, 1984; for reviews). Acquisition of the opponent process by the backward conditioning procedure has also been demonstrated in rats’ taste learning with emetic drugs (i.e., conditioned taste preference rather than taste


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aversion), if the drug–taste trial was repeated in training (Barker and Weaver, 1991; Green and Garcia, 1971; Hasegawa, 1981). Furthermore, Salvy et al. (2004) have demonstrated with a taste cue that wheel running yields conditioned aversion when it follows the target taste intake (i.e., forward conditioning), but conditioned preference when it precedes the target taste intake (i.e., backward conditioning). Hughes and Boakes (2008) recently replicated their results with much more robust data set. Accordingly, the administration of forward pairings of a chamber CS and a running US is necessary to decide whether a primary effect of wheel running is rewarding or not. In the experiment reported below, rats received forward pairings of a chamber CS with a running US and isolated exposures to the other chamber. After this differential conditioning, the rats’ preference/aversion to these chambers was assessed in a choice test between them. Because the present study appears to be the first experiment on forward chamber–running conditioning, we prepared two US lengths and one of them (a 20- or 60-min running opportunity) was employed for the separate groups. 2. Method 2.1. Subjects The subjects were 32 experimentally na¨ıve male Wistar rats maintained on an ad-lib food schedule in the individual hanging home cages on a 12:12 h light–dark cycle (lights on at 8:00 a.m.) at about 23 ◦ C. Water was limited to 30 min per day in the home cage for 3 days before the beginning of the experimental protocols. This water-deprivation condition was maintained during the experiment, when 30-min water access was available in the home cages 90 min after the daily confinement in a chamber CS. 2.2. Apparatus The conditioning and testing were administered in a conventionally illuminated experimental room having two place conditioning boxes, four running wheels, and four small plastic cages. Each of the two place conditioning boxes (30 cm height, 30 cm width, and 80 cm length) consisted of two joined 40-cm long Plexiglas chambers that had walls of black-and-white stripes (3 cm band width). One chamber had three walls of horizontal stripes and a stainless wire mesh floor, while the other had three walls of horizontal stripes and a perforated aluminum floor. The ceilings of these chambers were transparent Plexiglas. The chambers were divided by a removable partition, which had the horizontal stripes and the vertical stripes on each side to make the fourth wall of each chamber during the conditioning. Each of the four activity wheels (FRW-30, Melquest, Japan) was identical to those employed by our previous research (Masaki and Nakajima, 2006). The inner dimensions of each wheel were 9 cm wide and 32 cm in diameter, and the floor was made of 0.5 cm metal rods spaced 1.1 cm apart. Although it could be driven by an electric power motor and had a side cage, the motor was turned off and only the wheel compartment was employed for the present purpose. A full turn of the wheel was automatically counted by a microswitch. Each of the four small cages (13 cm height, 17–20 cm width and 27–30 cm length) had a clear plastic floor and walls, and a stainless wire mesh roof. 2.3. Procedure All experimental sessions were conducted at the same time (the light condition) of successive days. The rats were initially assigned

to one of four groups of eight rats each matched for their bodyweights of the day before the training: the means (S.E.s) were 262.8 (2.1), 257.3 (5.2), 258.8 (3.5), and 256.8 (2.7) g, respectively, for Groups H-Run20, V-Run20, H-Run60, and V-Run60. Group names stand for the target CS chamber (horizontal or vertical) to be paired with running and the length of the outcome (20 or 60 min). Differential conditioning training was conducted for 8 days. Daily training began with a period of 10-min confinement to either the horizontal chamber (H) or the vertical chamber (V). The confinement in a target chamber was immediately followed by placing in the activity wheel. On the other days, the rats were confined in the non-target chamber for 10 min, and then were immediately placed in the individual small plastic cages: the placing in the small cage was employed here as the control treatment to reduce the possibility that the novelty of any apparatus was the critical US for establishing learning. The length of each outcome treatment (i.e., placing in the wheel or in the small cage) was 20 or 60 min. We daily administered four squads of eight rats consisting of two rats from each of the four groups. Within each squad, a chamber–outcome pairing in rats of the 20-min groups was conducted while rats of the 60-min groups were receiving the outcome treatment. With this protocol, we could complete the daily work within 5 h (70 min × 4 squads = 280 min). The 8-day training sequences employed were HVVHHVHV for half of the rats in each group, and VHHVVHVH for the other half. Conditioned reactions to the chamber were assessed on a subsequent day by a choice test. The partition was removed from the conditioning box, and each rat was placed at the center of the box with the body along the midline (i.e., the annex line of the two chambers), and then given free access to both horizontal and vertical chambers for 10 min. The time spent in each chamber during testing was recorded by a video camera, which was located above the place conditioning box. A rat was considered to be in a chamber when all four paws were in that chamber. Because there were only two conditioning boxes, we repeated the procedure 16 times to administer a choice test for all of the 32 rats in a balanced order with respect to the group assignments. All statistical decisions were based on the alpha level set at p < 0.05. 3. Results 3.1. Wheel running Each rat was given four opportunities to run in the wheel during the differential conditioning training. The number of wheel revolutions during the four training sessions is displayed in Table 1. All groups increased wheel turns over sessions, and, as expected, the rats given 60-min running opportunities produced more wheel turns than did the rats given 20-min running opportunities. A 2 × 2 × 4 analysis of variance (ANOVA) applied to the data, with outcome length (20 or 60 min) and target chamber identity (H-Run or V-Run) as between-subject factors and session as a within-subject factor, supported these impressions: the main effects of duration, F Table 1 Mean (S.E.) numbers of wheel turns in each group for differential conditioning training Group

H-Run20 V-Run20 H-Run60 V-Run60

Training session 1




58.38 (13.33) 79.75 (14.88) 113.13 (16.52) 127.88 (18.75)

68.13 (9.51) 105.88 (12.63) 142.38 (18.01) 153.13 (21.08)

86.50 (11.26) 126.5 (15.18) 155.38 (17.30) 167.25 (18.85)

82.88 (10.11) 115.25 (16.22) 142.38 (17.47) 172.75 (30.00)

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(1, 28) = 13.58, p < 0.001, and session, F (3, 84) = 15.87, p < 0.001, were significant. Although Table 1 indicates that the number of wheel turns were less in Group H-Run20 than that in Group V-Run20, this impression was not confirmed by the aforementioned ANOVA, that yielded no significant main effect of target, F (1, 28) = 2.65, p = 0.11, or interactions, Fs < 1.

min wheel running endowed rats with aversion to the chamber paired with the running. But, there was no significant difference between Groups H-Run20 and V-Run20, F < 1.

3.2. Choice testing

In the present study, we employed a forward conditioning procedure with a place cue as a CS and wheel running as a US. Confinement of a rat in one of two distinctive chambers was followed by a 20- or 60-min running opportunity, while the other was followed by placing in the small cage for an equivalent period. The subsequent choice test demonstrated that the rats given 60min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. Namely, as in the case with forward conditioning with taste cues (e.g., Lett and Grant, 1996), wheel running endowed aversive properties to the target chamber, resulting in conditioned place aversion. It may be worth pointing out that Masaki (submitted for publication) has recently found that swimming activity, which is another effective exercise US for taste aversion learning (e.g., Masaki and Nakajima, 2005, 2006; Nakajima and Masaki, 2004), also endows conditioned place aversion in a forward conditioning procedure. The present experiment used water-deprived rats, because the demonstrations of running-based place preference with backward conditioning procedures also employed water-deprived rats (Lett et al., 2001b) or food-deprived rats (Belke and Wagner, 2005; Lett et al., 2000, 2001a, 2002). Water- and/or food- deprived rats have been commonly used in running-based taste aversion and preference learning (e.g., Forristall et al., 2007; Hughes and Boakes, 2008; Lett and Grant, 1996; Nakajima, 2004; Nakajima et al., 2006; Salvy et al., 2004). Although effects of such drive operations on running-based taste/place learning deserve a scrutiny in future research, the drive operations seem not essential factors because of Lett et al.’s (1998) report that neither water nor food deprivation was necessary at least in running-based taste aversion learning. With taste cues and a 15-min running opportunity US, response differentiation emerged after six sessions (three sessions for each cue) in our previous study (Nakajima et al., 2000). The failure to detect place aversion based on four 20-min running opportunities in the present study, thus, might imply that running-based place aversion is generally harder to obtain than running-based taste aversion. However, because the amount of Pavlovian conditioning depends on the salience of cues (e.g., Kamin, 1965), the lack of place aversion learning with the 20-min running US may be due to the chamber cues employed in the present study. With much more discriminably different chamber cues, we might have obtained a reliable result of conditioned place aversion with the 20min running US. In any event, the stronger place aversion in the rats given 60-min running opportunities than in the rats given 20-min running opportunities agrees with the law of US strength in Pavlovian conditioning, which is also demonstrated in running-based taste aversion learning (Hayashi et al., 2002; Masaki and Nakajima, 2006). The present study was designed to test whether a primary effect of wheel running is rewarding or aversive when it is paired with a chamber CS. In accord with a number of studies with a taste CS (e.g., Lett and Grant, 1996; see Boakes and Nakajima, in press, for a review), forward pairings of a chamber CS and a running US resulted in avoidance of rather than preference for, the paired chamber. These forward aversive conditioning results, taken together with acquired preferences by backward conditioning with a chamber CS (Belke and Wagner, 2005; Lett et al., 2000, 2001a,b, 2002) and a taste CS (Hughes and Boakes, 2008; Salvy et al., 2004), agree with the predictions from the opponent-process theory of moti-

The most important data were the mean times spent in each chamber in the 10-min choice test as illustrated in the top panel of Fig. 1. Because the rats could stay in the midline of the box, the times in the horizontal and vertical chambers are not complementary. The rats given 20-min running opportunities spent slightly more time in the horizontal chamber than in the vertical chamber regardless of the target identity, suggesting an unconditioned preference for the horizontal chamber over the vertical chamber. However, the rats given 60-min running opportunities spent less time in the running-paired chamber than in the unpaired chamber. The results may be better understood in the choice preference ratio. The bottom panel of Fig. 1 depicted the mean percentage of time spent in the horizontal chamber relative to the total time spent in both chambers. The lower this score, the stronger aversion to the horizontal chamber estimated. A 2 (length) × 2 (target identity) ANOVA applied to the data summarized in this panel yielded a significant length × target interaction, F (1, 28) = 5.29, p < 0.03, but the main effects of length, F (1, 28) = 2.10, p = 0.16, and target, F (1, 28) = 1.41, p = 0.24, were not significant. Subsequent simple main effect analyses revealed that Group H-Run60 had a significantly lower score than Group V-Run60, F (1, 28) = 6.08, p = 0.02, suggesting that 60-

Fig. 1. Performance of rats in the choice test. Top panel shows the mean time spent in the horizontal chamber and the vertical chamber. The bottom panel presents the mean percentage of time spent in the horizontal chamber relative to total time spent in the both chambers. Error bars indicate S.E. H-Run: horizontal-running; VRun: vertical-running. The opportunity of running in the activity wheel was 20 or 60 min.

4. Discussion


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vation (Schull, 1979; Solomon, 1980; Solomon and Corbit, 1974) or its derivative, the sometimes-opponent-process (SOP) model (Wagner, 1981; Wagner and Larew, 1985).

5. The opponent-process analysis of the affective value of running According to the opponent-process theory (Schull, 1979; Solomon, 1980; Solomon and Corbit, 1974), an US quickly evokes a direct component called the “a-process,” which in turn slowly activates a counteractive component called the “b-process.” The affective experience of animals is a product of these opponent processes, but the a-process overcomes the b-process to yield the excitatory “A-state” during the US presentation. After the US offset, however, the a-process swiftly goes to zero, while the b-process decays slowly, resulting in long-lasting inhibitory “B-state.” Thus, if a CS is paired with the A-state in a forward CS–US conditioning procedure, the CS acquires an excitatory property, while a backward US–CS pairing endows the CS with conditioned inhibition because the animal is in the B-state when the CS arrives. Assuming the Astate of wheel running as aversive and its B-state as rewarding, the opponent-process theory easily explains the forward aversive conditioning and backward hedonic conditioning with taste and chamber CSs noted above. The application of the opponent-process theory to conditioning with a running US is not a bizarre idea, because the exponent of the theory himself has included jogging and marathon running in everyday examples explained by the theory (Solomon, 1980). The opponent-process theory also assumes that repeated stimulations strengthen the b-process but not the a-process. With this postulate, the theory can account for the recent finding by Hughes and Boakes (2008) that previous running experience alleviates subsequent taste aversion learning caused by forward conditioning with taste–running pairings and facilitates subsequent taste preference learning caused by backward conditioning with running–taste pairings (see Overmier et al., 1979, for similar opposite effects of US preexposures on dogs’ forward and backward conditioning with a shock US): because of the developed “b-process” by the previous running, the aversive A-state is weak and the rewarding B-state is strong when the animals enter the conditioning phase. Speculations about the running-induced affective states from the opponent-process viewpoint lead to the prediction that longterm preexposure to running alleviates subsequent place aversion learning by chamber–running pairings (i.e., forward conditioning) and facilitates place preference learning by running–chamber pairings (i.e., backward conditioning). In other words, the finding of Hughes and Boakes (2008) with a taste CS should be replicated with a chamber CS. Another, much more intriguing prediction from the opponent-process theory is that continuing forward conditioning with a running US would yield a post-asymptotic decrease in conditioned taste/place aversion (see Overmier et al., 1979, for a similar effect on dogs fear conditioning). On the other hand, taste/place preference produced by backward conditioning should be a monotonic function of the number of US–CS trials. Parenthetically, Jennings and McCutcheon (1974) reported that running-induced sucrose suppression decreased over sessions, although the authors did not consider the sucrose suppression as conditioned taste aversion. A difficulty of the opponent-process view of the affective properties of wheel running is that, as noted in the introduction of the present article, rats’ instrumental responses are positively reinforced by the following running opportunity (e.g., Belke, 1996, 1997; Kagan and Berkun, 1954; Iversen, 1993; Livesey et al., 1972). Namely, wheel running is rewarding despite the aversive A-state

is supposed to follow the instrumental responding. This difficulty might be explained by the fact that in these studies rats had been pretrained to run before the conditioning phase (but see Collier and Hirsch, 1971, for an exception), so that in the subsequent conditioning phase the instrumental responding was seemingly followed by the immediate but weakened aversive A-state and the delayed but strengthened hedonic B-state. If the punitive effect by the A-state is negligible, the responding should be reinforced by the delayed B-state. The delayed reinforcement by the strengthened hedonic B-state might also account for the demonstration of conditioned place preference in golden hamsters by a simultaneous conditioning procedure (Antoniadis et al., 2000), because they had a running experience in the home cages (Antoniadis, personal communication, August 8, 2007). Acknowledgements This research was supported by a post-doc grant from the Japan Society for the Promotion of Science (JSPS) to the first author (#174433) and a grant for Scientific Research in Academic Frontier Promotion Project provided by the MEXT of Japan to the Research Center for Applied Psychological Science of Kwansei Gakuin University (KGU), to which the second author is also affiliated. The preparation of the manuscript was made available by a JSPS postdoc grant (#19-6826) to the first author, who is now at the Department of Psychology, Nagoya University, and a KGU sabbatical grant to the second author. The opponent-process interpretation of the data came to the second author when he was on the sabbatical leave at the University of Sydney, and developed by discussion with Robert A. Boakes, who also generously read and gave comments on the manuscript. References Antoniadis, E.A., Ko, C.H., Ralph, M.R., McDonald, R.J., 2000. Circadian rhythms, aging and memory. Behav. Brain Res. 111, 25–37. Barker, L.M., Weaver III, C.A., 1991. Conditioning flavor preferences in rats: dissecting the “medicine effect”. Learn. Motiv. 22, 311–328. Belke, T.W., 1996. The effect of a change in body weight on running and responding reinforced by the opportunity to run. Psychol. Rec. 46, 421–433. Belke, T.W., 1997. Running and responding reinforced by the opportunity to run: effect of reinforcer duration. J. Exp. Anal. Behav. 67, 337–351. Belke, T.W., Wagner, J.P., 2005. The reinforcing property and the rewarding aftereffect of wheel running in rats: a combination of two paradigms. Behav. Process. 68, 165–172. Boakes, R.A., Nakajima, S. Taste aversions based on running or swimming. In: Reilly, S., Schachtman, T.R. (Eds.), Conditioned Taste Aversion: Behavioral and Neural Processes. Oxford University Press, Oxford, UK, in press. Collier, G., Hirsch, E., 1971. Reinforcing properties of spontaneous activity in the rat. J. Comp. Physiol. Psychol. 77, 155–160. Forristall, J.R., Hookey, B.L., Grant, V.L., 2007. Conditioned taste avoidance induced by forced and voluntary wheel running in rats. Behav. Process. 74, 326–333. Green, K.F., Garcia, J., 1971. Recuperation from illness: flavor enhancement for rats. Science 173, 749–751. Hall, J.F., 1984. Backward conditioning in Pavlovian type studies. Pavlov. J. Biol. Sci. 19, 163–168. Hasegawa, Y., 1981. Recuperation from lithium-induced illness: flavor enhancement for rats. Behav. Neural Biol. 33, 252–255. Hayashi, H., Nakajima, S., Urushihara, K., Imada, H., 2002. Taste avoidance caused by spontaneous wheel running: effects of duration and delay of wheel confinement. Learn. Motiv. 33, 390–409. Hughes, S.C., Boakes, R.A., 2008. Flavor preferences produced by backward pairing with wheel running. J. Exp. Psychol.: Anim. Behav. Process. 34, 283–293. Iversen, I.H., 1993. Techniques for establishing schedules with wheel running as reinforcement in rats. J. Exp. Anal. Behav. 60, 219–238. Jennings, W.A., McCutcheon, L.E., 1974. Novel food and novel running wheels: conditions for inhibition of sucrose intake in rats. J. Comp. Physiol. Psychol. 87, 100–105. Kagan, J., Berkun, M., 1954. The reward value of running activity. J. Comp. Physiol. Psychol. 47, 108. Kamin, L.J., 1965. Temporal and intensity characteristics of the conditioned stimulus. In: Prokasy, W.F. (Ed.), Classical Conditioning: A Symposium. Academic Press, New York, New York, pp. 118–147.

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