Bingeing in rats: Persistence of high intakes of palatable solutions induced by 1-in-4 days intermittent access

When animals are given access to a palatable food or drink on some days but not on others, the amount they consume can far exceed the daily amounts consumed by controls given daily access. In a previous study such bingeing was found when rats were given 4% sucrose solution; it also found that, following 1-in-4-days access for many weeks, intakes remained persistently higher than that of controls even when the conditions were changed to 1-in-2-days access for both groups. One aim of the three experiments reported here was to test whether such persistent bingeing could be found for other solutions. This was confirmed in rats for a saccharin solution and a highly palatable saccharin-plus-glucose solution. However, when a maltodextrin solution was used, initial increased intakes produced by the 1-in-4-days schedule were not maintained when this was changed to a 1-in-2-days schedule. These results suggested that the hedonic value of a solution is more important than its caloric content in determining whether it will support persistent bingeing. A second aim was to test for evidence that the 1-in-4-days procedure induced an addiction to the target solution. No such evidence was found using multiple measures including instrumental responding and anxiety-like behavior on the elevated plus-maze for craving and withdrawal respectively.


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Binge eating can be defined as the consumption of a large amount of food in a short period 46 of time (APA, 2013). In humans it can lead to detrimental consequences to individuals' physical and psychological well-being. For example, binge eating is associated with a loss of 2.1.4 Procedure 248 An outline of the procedure for Experiment 1 is summarized in Table 1.  253 After five days of acclimatization and handling, the pre-diet phase began with chow 254 restricted to 85 g per group cage per day, given after daily lever-press sessions and with water 255 always available, except for 1 h before sessions.  Each rat was then given lever-press training using continuous reinforcement (FR-1). 264 Training was considered successful when a rat made at least 25 lever presses within a session. 265 Up to 18 sessions were given, and data from rats failing this criterion were excluded from 266 Group (n = 10) For the initial training session, each rat was given a single bottle containing a 4% sucrose  As suggested by the mean daily chow intakes and body weights shown in Table 2, no 341 group differences in chow intake were detected either during Phase 1 or Phase 2 (ps > .10).

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There was a linear increase in body weight across the experiment (linear trend p < .001), but 343 at similar rates between the groups, with no group differences in body weight found either at 344 the end of Phase 1 or end of Phase 2 (Fs < 1).  The Binge group showed a linear trend in sucrose intake, F(1, 9) = 11.82, p = .007, which 359 was not found in the Unrestricted group, F < 1, confirming that the Binge group escalated 360 their sucrose intake across Phase 1, whereas the Unrestricted group did not.
Phase 2. Sucrose intakes in the Binge group decreased over the first three days of Phase 2, 362 before returning to the elevated sucrose intakes found at the end of Phase 1 (see Figure 1).

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The Unrestricted group increased their sucrose intake across Phase 2 but continued to 364 maintain lower intakes than the Binge group throughout the 28 days of alternate-day access.

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The 2 x (13) Group x Day mixed ANOVA revealed a significant linear trend in sucrose     Almond preferences are shown in Figure 2A.

Sucrose preference 418
Mean sucrose preference data are shown in Figure 2B. The intra-class correlation coefficient was .99, p < .001, indicating high inter-rater Forty experimentally-naïve male Sprague-Dawley rats from the same source as 516 Experiment 1 were six weeks old, with an average weight of 308 g (range 285-330 g), on 517 arrival and were initially group-housed (n = 5/cage). As previously, the temperature-and 518 humidity-controlled colony room was maintained on a reversed 12-h light/dark cycle (lights 519 off at 0900 hrs). After two days of acclimatization and handling, the Pre-diet Phase began 520 with chow and water restrictions identical to those described for Experiment 1. Other details 521 were the same as described for Experiment 1. .4% (w/v) pure (acid-free) saccharin solution (Sigma-Aldrich, 240931). The apparatus was identical to that used in Experiment 1. The timeline of Experiment 2 is outlined in Table 3. Table 3. Experimental design of Experiment 2. *Maltodextrin Binge n = 9 in Phase 2 and 3.   At the start of this phase rats in the Maltodextrin condition were allocated to two groups 569 (n = 10/group) matched primarily for body weight and almond preference but also to a lesser 570 degree for sucrose preference and lever-press responding. the last 3 days of Phase 1 (see Figure 3). Consequently, only Phase 1 data will be reported 582 here for the SB and SU groups.  press sessions over three successive days (one session/day), using the following 601 reinforcement schedules: VI-10s, VR-5, VR-5. The average number of lever presses over the 602 two VR-5 sessions was taken as the after-withdrawal measure of lever-press responding. On

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Day 91 rats were tested for almond preference using the two-bottle choice test procedure.

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The next day rats were also tested for preference for maltodextrin over 4% sucrose solution 605 as previously described. During these test days, rats were given 2-h daily chow access at 606 1400 hrs (after their daily lever-press session or two-bottle choice test). Rats were returned to ad libitum chow on Day 93 before EPM testing. On Day 94 each rat was tested on the EPM 608 following the procedure described for Experiment 1. Behavior on the EPM was scored and 609 calculated as described for Experiment 1. To establish inter-rater reliability, ten EPM 610 recordings were also rated by a blind scorer and intra-class reliability between the two sets of 611 ten scores was measured. ANOVAs. Since motivational states may have differed across tests of lever-pressing and 619 flavor preferences due to differences in the degree of food deprivation, overall changes across 620 tests were not considered meaningful and consequently only data from after-withdrawal tests 621 were analyzed using one-way ANOVAs. to consume almost twice the amount of saccharin relative to SU rats.  In summary, no differences were found between the MB and MU group on any of the 691 behavioral measures. A one-way ANOVA applied to lever-press rates did not find any Group 692 effect (F <1), indicating that both MU and MB groups exhibited similar lever-press 693 responding after withdrawal. Mean almond preference data are shown in Figure 4A.      The timeline of Experiment 3 is outlined in Table 5.  800 After acclimatization and handling, daily water access was gradually reduced across four 801 consecutive days from 4 h, to 2 h, 1 h, and 30 min, in preparation for water training in the 802 drinking chambers. Rats were given 30-min access to water after each water training session.

803
Water training (Days 1 -3). Rats were transferred from their home cages to the 804 individual drinking chambers where they were given 30-min access to water in each daily 805 training session. On Day 1 rats were given a single bottle, whereas on Days 2 and 3 rats were  included as a factor for the behavioral data in Experiment 3 because rats were sated during 877 both pre-and post-diet tests.  by Access interaction effect, F(6, 216) = 6.759, p < .001. As Figure 5 suggests, these main  across Phase 2 in contrast to steady intakes in the GSB and SB groups.   Almond preferences are shown in Figure 6A. A 2 x 2 x (3) Solution x Access x Test 946 mixed ANOVA failed to detect any main effects of Solution, Access, Test or interaction 947 between these factors (all ps > .05).  Access by Test interaction (Fs < 1), indicating that there were no differences in the decrease 953 in preference for saccharin over sucrose across tests between the SU and SB groups ( Figure   954 6B). For the GSU and GSB groups, no main effects nor interactions were found (ps > .10), 955 indicating that preference for the glucose + saccharin solution relative to sucrose remained 956 consistent across tests ( Figure 6C). 29.0% in the GSU group, and 30.4% in the GSB group. These percentages are higher than 961 those obtained in the previous experiment and suggest that the present rats were not anxious.

962
Inter-rater reliability analyses were not run because no group differences were found.

979
The current experiment demonstrated that the persistent binge effect found in Experiment 980 1 could also been found when using a sweet, but non-caloric saccharin solution and a highly

1001
The current study had two main aims. One was to establish whether the persistence of 1002 binge-like consumption induced by the adapted Eikelboom protocol would generalize to 1003 similarly attractive solutions. The second was to test whether persistent bingeing would be 1004 accompanied by addiction-like behaviors. As discussed in more detail below, the first aim 1005 was achieved but no evidence was obtained to indicate that the 1-in-4-days binge treatment 1006 produced addiction to any of the solutions used in the three experiments. escalation in 24-h intake across exposures and that these elevated intakes persisted when 1009 switched to alternate-day access, even when the duration of Phase 1 at 28 days was shorter current study, some support for intermittent access increasing hedonic value was found in