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Experimental and Clinical Psychopharmacology
Physical Activity Reduces Alcohol Consumption Induced by Reward
Downshift
Elena Castejón, Esmeralda Fuentes-Verdugo, Ricardo Pellón, and Carmen Torres
Online First Publication, June 20, 2022. http://dx.doi.org/10.1037/pha0000587
CITATION
Castejón, E., Fuentes-Verdugo, E., Pellón, R., & Torres, C. (2022, June 20). Physical Activity Reduces Alcohol Consumption
Induced by Reward Downshift. Experimental and Clinical Psychopharmacology. Advance online publication.
http://dx.doi.org/10.1037/pha0000587
Physical Activity Reduces Alcohol Consumption
Induced by Reward Downshift
Elena Castejón
1
, Esmeralda Fuentes-Verdugo
1
, Ricardo Pellón
1
, and Carmen Torres
2
1
Departamento de Psicología Básica I, Facultad de Psicología, Universidad Nacional de Educación a Distancia (UNED)
2
Departamento de Psicología, Universidad de Jaén
Increased voluntary consumption of alcohol and other anxiolytics has been demonstrated in animals after
experiencing frustrative reward devaluation (downshift) or omission. These results have been interpreted in
terms of emotional self-medication. In the present study, we analyzed whether voluntary physical activity
reduces alcohol intake induced by reward downshift. Sixty-four male Wistar rats were divided into eight
groups (n=8). Thirty-two (downshifted) animals received 32% sucrose during 10 preshift sessions (5 min),
followed by 4% sucrose during five postshift sessions, whereas 32 (unshifted) controls were always exposed
to 4% sucrose. Immediately after each consummatory session, animals were exposed to a 2-hr two-bottle
preference test involving 32% alcohol versus water or water versus water. Half of the animals had also
access to a wheel for voluntary running during the preference test. The results showed lower sucrose
consumption in downshifted groups compared with unshifted controls (the frustrative reward downshift
effect). Reward downshift significantly increased alcohol intake, this effect being absent in downshifted
animals with access to the wheel. These findings suggest that physical exercise could be useful to prevent
alcohol self-medication induced by frustrative nonreward.
Public Health Significance
Human and nonhuman studies suggest that consumption-dependent reduction in negative affect
promotes alcohol intake. This “self-medication behavior”has been observed in frustrating situations
involving reward loss. This study showed (in rats) that increased alcohol intake induced by a reward
devaluation event was abolished by voluntary wheel running. Physical exercise could therefore be useful
to prevent the maladaptive effects of frustration on drug use.
Keywords: alcohol consumption, emotional self-medication, frustration, physical activity, reward
downshift
The consumption of psychoactive substances is a deeply rooted
human practice since ancient times. Occasionally, such practices can
develop into maladaptive patterns characterized by a compulsive
tendency to search and consume a substance, a loss of control for
limited consumption, and the emergence of a negative emotional
state when access to the drug is not possible (Koob, 2021).
Several different neurobehavioral approaches have been pro-
posed to explain why people use drugs and eventually develop a
substance use disorder. Most of them focus on the (dopamine
mesolimbic-dependent) acute pleasant/reinforcing properties of
psychoactive substances (Di Chiara & Bassareo, 2007;Koob,
2014;Uhl et al., 2019). The emotional self-medication hypothesis,
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This article is intended solely for the personal use of the individual user and is not to be disseminated broadly.
Carmen Torres https://orcid.org/0000-0001-8573-0990
This research was supported by national grants from the Ministerio de
Economía y Competitividad (Grant PSI2017-87340-P), Consejería de Econ-
omía, Innovación, Ciencia y Empleo, Junta de Andalucía (Grant HUM-642),
Universidad de Jaen (Grant SCAI, Action Plan 1) to Carmen Torres and
Universidad Nacional de Educación a Distancia (Grant 2021V/PREMIO/04)
to Ricardo Pellón. All authors contributed in a significant way to the article
and that all authors have read and approved the final article. All authors
declare that they have no conflicts of interest. The authors wish to thank
Antonio Rey for excellent technical support.
All data, analysis code, and research materials will be available by
emailing the corresponding author. This study’s design and its analysis
were not preregistered.
Elena Castejón played lead role in investigation and equal role in
conceptualization, data curation, formal analysis, methodology, software,
visualization, writing of original draft, and writing of review and editing.
Esmeralda Fuentes-Verdugo played supporting role in conceptualization,
data curation, formal analysis, investigation, and methodology and equal
role in software, supervision, writing of original draft ,and writing of review
and editing. Ricardo Pellón played lead role in conceptualization; support-
ing role in investigation, supervision, and validation; and equal role in data
curation, formal analysis, funding acquisition, methodology, project admin-
istration, resources, visualization, writing of original draft, and writing of
review and editing. Carmen Torres played lead role in conceptualization,
funding acquisition, and project administration; supporting role in supervi-
sion, validation, and visualization; and equal role in data curation, formal
analysis, methodology, writing of original draft, and writing of review and
editing.
Correspondence concerning this article should be addressed to Carmen
Torres, Departamento de Psicología, Universidad de Jaén, Campus
Lagunillas s/n, 23071 Jaén, Spain. Email: mctorres@ujaen.es
Experimental and Clinical Psychopharmacology
© 2022 American Psychological Association
ISSN: 1064-1297 https://doi.org/10.1037/pha0000587
1
however, suggests that the type of substance chosen for consump-
tion depends on the extent to which that substance alleviates a range
of negative affective states (Khantzian, 1985,2013;Torres &
Papini, 2016). According to this view, some clinical studies suggest
that drug-use behavior is reinforced by a reduction in negative affect
present in a variety of psychiatric and psychological conditions
(Castaneda et al., 1994;DeMartini & Carey, 2011;Enman et al.,
2014;Menary et al., 2011;Robinson et al., 2011), triggered by
negative life events (Konopka et al., 2013;McPhee et al., 2020),
and associated with drug withdrawal (Koob et al., 2020;Koob &
Volkow, 2016). Additional support for the emotional self-
medication hypothesis derives from survey studies indicating that
consumption-dependent reduction in negative affect is frequently
cited as a factor promoting alcohol intake, among other drugs (e.g.,
Adams et al., 2012;Rodriguez et al., 2020). However, some studies
have found weak associations between stress and drug use (Preston
& Epstein, 2011), lack of relationships between high levels of
emotional distress and reported substance use (Hall & Queener,
2007), moderate prevalence rates of self-medication with alcohol
and other drugs among individuals suffering from mood and anxiety
disorders (Turner et al., 2018), no evidence of improvement in
anxiety symptoms after drug consumption (Carrigan & Randall,
2003), and associations between substance use and symptoms
exacerbation (Brady et al., 1990). These inconsistent results reveal
the complexity of the relationship between aversive events/negative
affect and drugs and alcohol intake, and the involvement of factors
other than emotional regulation in drug intake.
Tests of the emotional self-medication hypothesis in nonhuman
animals show that a number of physical and psychological aversive/
stressing stimuli lead to increased voluntary alcohol drinking in
rodents, although inconsistencies have also been reported (Becker
et al., 2011;Sillaber & Henniger, 2004;Spanagel et al., 2014).
Recent studies have extended these results to situations involving
frustrative reward loss, that is, the sudden and unexpected reduction
or omission of an expected reward (Amsel, 1992;Gray, 1987). In
these studies, animals are exposed to two tasks in tandem: an
induction task eventually involving reward loss, followed each
day by a preference test providing a choice between an anxiolytic
solution (e.g., alcohol) and water. In one study (Manzo et al., 2014),
animals with extreme differences in emotional reactivity and anxiety
(Roman high- and low-avoidance inbred rat strains: RHA-I and
RLA-I; Fernández-Teruel et al., 2021) were exposed to appetitive
(consummatory and instrumental) acquisition and extinction. In-
mediately after each session, rats were exposed to an alcohol (2%)
versus water, two-bottle preference test. Anxious RLA-I rats
showed greater preference and consumption of alcohol than less
anxious RHA-I rats after extinction (reward omission) sessions.
Another study tested the effect of reward downshift (from 32% to
4% sucrose) in a consummatory task on the voluntary consumption
of alcohol and the benzodiazepine anxiolytic chlordiazepoxide in
Wistar rats. Again, animals increased anxiolytic consumption after
reward downshift sessions, an effect that was not observed in
unshifted groups (always receiving access to 4% sucrose), and in
downshifted and unshifted groups exposed to water during the
preference test (Manzo, Donaire, et al., 2015; see also Donaire
et al., 2022). Increased alcohol intake seemed to depend on its
anxiolytic properties, as increased alcohol consumption observed
after experiencing reward devaluation was accompanied by signs of
anxiolysis in a test for anxiety administered immediately after the
alcohol preference test (higher head-dipping frequency in the hole-
board test; Donaire et al., 2020). Interestingly, the augmented
alcohol intake induced by reward loss was absent in animals
receiving partial reinforcement training before experiencing the
reward loss event (Manzo, Gómez, et al., 2015), therefore suggest-
ing that the impact of the frustrative induction task on drug intake
can be prevented by treatments that increase resistance to frustration
(Amsel, 1992). The present experiment aimed at extending this
finding by identifying additional experimental manipulations to
reduce or abolish the increased alcohol consumption induced by
reward loss.
Physical activity has been extensively used as an adjunctive
intervention for substance use disorders based on its physical and
mental health benefits (Georgakouli et al., 2017;Jensen et al., 2019;
Roessler, 2010;Weinstock et al., 2017), some of them dependent on
its decreasing effects on negative affect (Abrantes et al., 2019; see,
however, Cabé et al., 2021, for inconsistent results). Additional
evidence from nonhuman animals’studies has shown reduced
alcohol intake in subjects with previous or simultaneous access
to alcohol and a wheel for voluntary running (Darlington et al.,
2016;Ehringer et al., 2009;Engelhart et al., 1992;McMillan et al.,
1976,1995), although negative results have also been found (Crews
et al., 2004;Ozburn et al., 2008). Importantly here, 1 hr of access to
a running wheel three times per week reversed the increase in
alcohol intake induced by social stress in mice, thus showing an
effect of physical activity on alcohol consumption induced by
aversive stimuli (Reguilón et al., 2020). In the present study, we
investigated whether these results extend to aversive situations
involving reward loss. To this aim, animals were exposed to a
frustrative induction task (32%-to-4% vs. 4%-to-4% sucrose), fol-
lowed daily by a free-choice alcohol (32%) versus water preference
test. Half of the animals also had access to a wheel for voluntary
running during the preference test. According to the evidence
previously reviewed, we predicted the following: (a) suppressed
sucrose consummatory behavior in downshifted (32-4) animals
relative to unshifted (4-4) animals, (b) higher alcohol intake and
preference in downshifted animals receiving alcohol in comparison
with controls (unshifted rats with access to alcohol and downshifted
rats with access to water), (c) reduced alcohol intake in downshifted
animals with access to a wheel for running during the preference test
compared with downshifted rats whose wheel was blocked.
Method
Subjects
The subjects were 64 experimentally naïve male Wistar rats (70
days; Envigo, Barcelona, Spain), weighing on average 318.55 g
(±33.83 g) at the beginning of the experiment. The number of
animals per group (n=8) was determined by a priori power analyses
based on sucrose consumption data obtained in our laboratory. Rats
were housed individually in polycarbonate cages (18 cm ×32 cm ×
20.5 cm, L×W×H) with water and environmental enrichment
continuously available, in a room with constant temperature (18 °C–
22 °C) and humidity (50%–60%), with lights on between 08:00 and
20:00 hr. Animals were food deprived and maintained within 82%–
85% of their ad lib weight. The experiment followed the national
directive guidelines for the use of animals in research and was
approved by the research ethics committee of the psychology faculty
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2CASTEJÓN, FUENTES-VERDUGO, PELLÓN, AND TORRES
of our university. All the manipulations, measures, and data in the
study are reported. No animals were omitted from the study, and all
animals completed the training sessions. All data, analysis code, and
research materials will be available by emailing the corresponding
author. This study’s design and its analysis were not preregistered.
Apparatus
Reward downshift training involved eight original Letica model
(LI 836) boxes customized by Cibertec (Madrid, Spain), each mea-
suring 29 cm ×24.5 cm ×35.5 cm (L×W×H). The back wall had a
3.2 cm ×3.9 hole throughwhich a metallicsipper tube of a graduated
cylinder was inserted. Boxes were placed inside a standard light–
sound absorbing enclosure. Licking response was automatically
registered with MED-PC-IV program for Windows 7 in a computer
located in the same room. The 32% (or 4%) sucrose solution was
prepared wt/wt by mixing 32 g (or 4 g) of sucrose for every 68 g
(or 96 g) of distilled water. These concentrations were selected on
the basis of previous studies showing that this reward discrepancy is
optimal to obtain a robust and consistent reward devaluation effect
(e.g., Donaire et al., 2022;Flaherty, 1996;Papini & Pellegrini, 2006).
The preference test was conducted in an adjacent experimental
room with eight polycarbonate boxes measuring 21 cm ×45 cm ×
24 cm (L×H×W), each equipped with a sliding door to give access
to a 9 cm high ×34 cm diameter wheel running. Wheels were
located in the right side of the boxes. Recording of the running
behavior (number of laps) was conducted with MED-PC program
for Windows 7 in a computer located in the same room. Fluid
consumption was measured by weighing the bottles (250 mL
polypropylene bottles with metallic nipple) before and after each
preference session (“Smart Weigh”Precision Scale, TS500). Alco-
hol (Ethanol 96% Extra Pure Ph Eur, Merck) was diluted in tap
water on a vol/vol basis. Each bottle contained 40 mL of alcohol
solution, prepared by mixing 166.66 (32%) mL of alcohol in 500 mL
of tap water. This alcohol concentration was selected based on the
increase in consumption after reward downshift observed in previ-
ous studies (Donaire et al., 2022) and because it led to consumption
levels in line with research on the pharmacological effects of alcohol
intake in rodents (e.g., Carnicella et al., 2011).
Procedure
Subjects were matched by weight, F<1, and randomly assigned
to Groups 32/Alcohol, 32/Alcohol +Wheel, 32/Water, 32/Water +
Wheel, 4/Alcohol, 4/Alcohol +Wheel, 4/Water, and 4/Water +
Wheel, respectively (n=8). For the induction task, a 5-min
habituation session in the consummatory box without fluids pre-
ceded sucrose consummatory training. On Days 1–10 (preshift
phase), animals had free access to 32% (or 4%) sucrose. On
Days 11–15 (postshift phase), all animals received 4% sucrose.
Each session lasted 5 min starting from the first contact with the
sipper tube. Rats were transported in squads of eight animals, one
from each experimental condition. The dependent variable was lick
frequency (number of licks during the 5-min session).
Immediately after each sucrose consummatory session, rats were
tested in a 2-hr, two-bottle alcohol—32%—(or water) versus water
preference test. Animals were first habituated for 4 days to the two-
bottle procedure with both bottles containing tap water (see Manzo,
Donaire, et al., 2015). All bottles were weighed before and after the
preference test to assess the amount of fluid consumed. The location
of the bottles was changed daily to minimize position preferences.
Half of the animals had access to the wheel for voluntary running
during the preference test, whereas in the other half, the wheel was
available but locked. The dependent variables were the amount of
alcohol (g) consumed transformed by the weight of the animal in the
same day (g/kg), and the number of wheel turns for each session. A
preference ratio for alcohol was also calculated by dividing the
consumption on each target bottle (alcohol or water, mL/kg) by the
total consumption for each preference test session. A preference
ratio above 0.5 reflects preference for alcohol over water and below
0.5 reflects preference for water over alcohol; 0.5 implies no
preference for either fluid. To calculate a preference ratio in groups
given access to water in both bottles, a bottle was arbitrarily
designated the target bottle for each animal.
Statistical Analysis
Analyses of variance were calculated for each dependent variable
with an αvalue set at the 0.05 level. Partial eta squared (η
2
) was used
to assess effect size. Preshift data were analyzed by calculating the
mean consumption for Sessions 8–10 (preshift terminal perfor-
mance, T). Sucrose intake (mL/kg), alcohol intake (g/kg), and
alcohol preference were subjected to a Contrast (32% vs. 4%) ×
Drug (alcohol vs. water) ×Wheel (with vs. without wheel) ×Session
(T, 11–15) analysis of variance, with session as a repeated measure
factor. Wheel running data were subjected to a Contrast (32% vs.
4%) ×Drug (alcohol vs. water) ×Session (T, 11–15) analysis of
variance. Planned Bonferroni comparisons were also calculated to
compare means of interest to the research (Castañeda et al., 1993),
so that we could answer questions such as whether or not a 32%-to-
4% sucrose devaluation induced consummatory suppression and
increased alcohol consumption and preference, and whether wheel
running prevented the increased alcohol consumption observed in
animals exposed to sucrose devaluation. To further test whether the
influence of wheel running on alcohol intake could be interpreted in
terms of response competition, Pearson’s correlation coefficients
were calculated between alcohol consumption (g/kg) and wheel
turns on every postshift session (p<.05). All statistical tests were
conducted with the IBM SPSS Statistics 27.0 package.
Results
Figure 1 shows the results of the induction task involving a 32%-
to-4% sucrose downshift during preshift (T) and postshift (11–15)
sessions.
A Contrast ×Drug ×Wheel ×Session analysis revealed a
statistically significant effect of contrast, F(1, 56) =8.396, p=
.005, η2
p=0.130, session, F(5, 280) =6.784, p=.0001, η2
p=0.108,
and a Contrast ×Session interaction, F(5, 280) =5.125, p=.0001,
η2
p=0.084. Bonferroni tests revealed statistically significant differ-
ences between downshifted (32) and unshifted (4) groups on post-
shift sessions 11, F(1, 56) =22.345, p=.0001, η2
p=0.285; 12, F(1,
56) =8.193, p<.006, η2
p=0.128; and 13, F(1, 56) =14.233, p=
.0001, η2
p=0.203. Therefore, regardless the drug (alcohol, water) or
the wheel (with, without) condition, animals exposed to sucrose
devaluation from 32% to 4% showed lower fluid intake of the
devalued 4% sucrose solution compared with animals receiving 4%
sucrose throughout training.
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EXERCISE, ALCOHOL INTAKE, AND FRUSTRATIVE NONREWARD 3
Table 1 shows the average of alcohol consumption (g/kg) across
sessions (T, Sessions 11–15) in groups receiving alcohol. In order to
analyze whether wheel running prevented increased alcohol intake
triggered by sucrose downshift, we focused on the terminal preshift
versus average postshift performance of unshifted (4) and downshifted
(32) groups with access to alcohol. As no effects of wheel were
obtained in unshifted controls, 4/Alcohol +Wheel versus 4/Alcohol,
F(1, 14) =0.363, p=.557, η2
p=0.025, Figure 2 presents the individual
and averaged results of Groups 32/Alcohol +Wheel and 32/Alcohol.
A Wheel ×Phase (T, post) analysis involving Groups 32/Alcohol
and 32/Alcohol +Wheel yielded a statistically significant effect of
Wheel, F(1, 14) =10.299, p=.006, η2
p=0.424. The Wheel ×Phase
interaction was marginally significant, F(1, 14) =3.654, p=.077,
η2
p=0.207. Importantly, only Group 32/Alcohol showed increased
alcohol consumption in postshift phase in comparison with preshift
phase, F(1, 14) =7.715, p=.015, η2
p=0.355. In addition, Group
32/Alcohol showed higher alcohol consumption compared with
32/Alcohol +Wheel only in postshift phase, F(1, 14) =7.900, p=
.014, η2
p=0.361.
The impact of reward devaluation and wheel access on alcohol
consumption was also analyzed in terms of alcohol preference
differences across alcohol groups and sessions (Figure 3).
A Contrast ×Wheel ×Session analysis showed statistically signifi-
cant main effects of session, F(5, 140) =3.280, p=.008, η2
p=0.105,
and wheel, F(1, 28) =16.168, p=.0001, η2
p=0.366. There were also
significant Session ×Contrast, F(5, 140) =2.370, p=.042, η2
p=
0.078, and Contrast ×Wheel, F(1, 28) =7.558, p=.010, η2
p=0.213,
interactions. To simplify the statistical analysis of these results, we
focused on analyzing whether alcohol preference in downshifted
animals was modulated by wheel running. There were statistically
significant differences between Groups 32/Alcohol and 32/Alcohol +
Wheel only in postshift sessions, Fs(1, 14) >5.630, ps<.034, η2
ps>
0.286. Moreover, alcohol preference was lower in preshift (T) phase in
comparison with postshift sessions 11, 12, and 13 in Group 32/Alcohol
(ps<.045), but not in Group 32/Alcohol +Wheel (ps>.230).
Figure 4 shows the number of wheel turns registered in down-
shifted and unshifted groups exposed to alcohol or water in the
preference test.
A Contrast ×Drug ×Session analysis revealed only a statistically
significant session effect, F(5, 140) =10.420, p=.001, η2
p=0.271,
thus showing an increase in wheel running across sessions regardless
the contrast (32% vs. 4%) or the drug (alcohol vs. water) condition.
Finally, statistically significant Pearson’s correlations between
alcohol intake (g/kg) and wheel turns were not obtained on
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Figure 1
Mean Number of Licks for Sucrose (±SEM) During the Preshift Phase (T, Average of the Last 3 Sessions, 8–10) and During the Postshift
Phase (Sessions 11–15) of the Induction Task
Note. SEM =standard error of the mean.
*Unshifted (4) groups versus downshifted (32) groups, p<.05.
Table 1
Mean (±SEM) Alcohol Consumption (g/kg) in Devalued Downshifted and Unshifted Groups Receiving Alcohol With and Without
Simultaneous Access to a Wheel for Voluntary Running
Group
Preshift phase Postshift phase
T 1112131415
32/Alcohol 3.86 (±0.61) 6.21 (±0.75) 9.33 (±3.57) 6.23 (±1.02) 8.84 (±3.33) 4.62 (±0.54)
32/Alcohol +Wheel 2.63 (±0.26) 2.38 (±0.33) 2.84 (±0.33) 2.96 (±0.41) 2.96 (±0.50) 2.42 (±0.45)
4/Alcohol 3.42 (±0.31) 4.61 (±0.57) 6.74 (±0.46) 3.69 (±0.46) 4.09 (±0.43) 7.25 (±3.77)
4/Alcohol +Wheel 3.18 (±0.34) 3.00 (±0.34) 7.44 (±4.38) 6.17 (±2.84) 3.07 (±0.51) 2.84 (±0.47)
Note. SEM =standard error of the mean; T =average of the last three sessions (8–10). Postshift sessions 11–15.
4CASTEJÓN, FUENTES-VERDUGO, PELLÓN, AND TORRES
postshift sessions, indicating no relation between measures of
drinking and running.
Discussion
In the present study, animals were exposed to a 32%-to-4%
sucrose downshift manipulation followed by access to alcohol
versus water for voluntary drinking with/without simultaneous
access to a wheel for voluntary running. We aimed at analyzing
whether physical exercise provided by a movable wheel would
reduce the augmented alcohol consumption repeatedly observed
after experiencing a reward loss event (Donaire et al., 2018,2020;
Manzo, Donaire, et al., 2015;Manzo et al., 2014). Compared with
unshifted (4) controls, downshifted (32) animals showed lower
sucrose consumption during the postshift (downshift) phase. Impor-
tantly, the augmented alcohol intake and preference (postshift >
preshift phase) registered in rats exposed to reward downshift was
absent in animals with simultaneous access to a wheel for running,
thus suggesting an attenuating effect of physical exercise on aug-
mented alcohol intake induced by reward loss.
The 32%-to-4% sucrose manipulation in the present experiment
negatively affected consummatory response regardless the subse-
quent drug (alcohol vs. water) or wheel (with, without) condition.
There is extensive behavioral, hormonal, pharmacological, psycho-
genetic, and neurobiological evidence indicating that animals
exposed to unexpected reward loss exhibit a behavioral impairment
that relies on the emergence of a negative emotional response
(referred to as frustration, disappointment, anxiety, or psychological
pain; see Amsel, 1992;Flaherty, 1996;Gray, 1987;Papini et al.,
2015). According to this view, forced administration of anxiolytics
(alcohol, benzodiazepines, barbiturates) before the reward down-
shift episode significantly attenuates consummatory suppression
(see Flaherty, 1996, for review). The finding that experiencing
reward downshift in turn increases subsequent voluntary anxiolytics
consumption also supports an interpretation of the reward downshift
effect in terms of negative emotion (Donaire et al., 2018,2020,
2022;Manzo, Donaire, et al., 2015; present results). Similar results
have been obtained with other reward loss and drug administration
paradigms (Ginsburg & Lamb, 2018;Podlesnik et al., 2006;
Vasquez et al., 2021), thus showing the usefulness of animal models
of reward loss to analyze the impact of negative emotions on drug
use and abuse.
The increase in alcohol consumption observed in animals
exposed to reward downshift may alternatively be explained in
terms of resurgence. This phenomenon refers to the recurrence or
recovery of a previously reinforced response when the reinforce-
ment for a more recently reinforced response is discontinued
(Bouton & Trask, 2016;Podlesnik et al., 2006;Shahan &
Sweeney, 2011). There is evidence in humans and nonhuman
animals that drug-seeking relapse can be precipitated by loss of
alternative nondrug reinforcement (Ginsburg & Lamb, 2018;
Podlesnik et al., 2006;Quick et al., 2011). According to this
view, 32/Alcohol animals increased alcohol intake as a way to
replace the reduction in reinforcement experienced from drinking a
downshifted sucrose solution. An interpretation of the present
results in terms of resurgence, however, has some limitations. First,
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Figure 2
Individual Data (Dashed Lines) and Mean ± SEM (Undotted Lines) of Alcohol Consumption (g/kg)
in the Preshift Phase (T, Average of the Last 3 Sessions, 8–10) and the Postshift Phase (Average of
the Sessions 11–15) of Groups 32/Alcohol and 32/Alcohol +Wheel
Note. SEM =standard error of the mean.
*T versus POST 11–15 (postshift sessions) in Group 32/Alcohol, p<.05. ** Group 32/Alcohol versus Group
32/Alcohol +Wheel in POST 11–15, p<.05.
EXERCISE, ALCOHOL INTAKE, AND FRUSTRATIVE NONREWARD 5
both the induction task and the preference test were consummatory
(rather than operant) and were presented consecutively in the same
day, rather than successively (in two differentiated training phases)
as used in the resurgence paradigm. Second, alcohol consumption
and preference increased from a baseline level, not from an absent
(previously extinguished) behavior. Finally, “resurgence”of alcohol
use would require evidence that alcohol was a source of reinforce-
ment (based on its pleasant effects), so that the “loss”of sucrose
increased behaviors (drinking) aimed at obtaining the alternative
reinforcer (32% alcohol). However, in the present experiment,
animals did not show preference for alcohol versus water in the
preshift phase (see T in Figure 3), a result that is consistent with
previous studies involving high doses of ethanol (Pautassi, 2019).
The increase in preference levels observed in Group 32/Alcohol
after experiencing reward downshift suggests that such preference
for alcohol was dependent on the reduction of negative affect
induced by sucrose devaluation.
The caloric contribution of the 32% alcohol solution could also
underlie the augmented alcohol consumption observed in food-
restricted animals exposed to a reduction in sucrose solution (from
32% to 4%). Nevertheless, a similar increase in fluid consumption
was observed in downshifted animals with subsequent access to a
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Figure 4
Mean Wheel Turns (±SEM) of the Groups With Access to a Running Wheel During the Preshift (T)
and Postshift Phases (11–15)
Note. SEM =standard error of the mean.
Figure 3
Mean (±SEM) Alcohol Preference Across Preshift (T) and Postshift Sessions (11–15) and in Groups
Receiving Alcohol
Note. SEM =standard error of the mean.
*Group 32/Alcohol versus Group 32/Alcohol +Wheel in postshift sessions, p<.05. ** Postshift sessions
versus T in Group 32/Alcohol, p<.05.
6CASTEJÓN, FUENTES-VERDUGO, PELLÓN, AND TORRES
solution containing chlordiazepoxide (Manzo, Donaire, et al.,
2015), an anxiolytic substance lacking caloric value. Alternatively,
anxiolysis derived from alcohol intake could rest on the ability of a
potent response (such as drinking) to interfere with the negative
emotional state induced by reward downshift, rather than on its
pharmacological properties per se (Papini & Dudley, 1997). How-
ever, downshifted groups with access to water showed no evidence
of change in fluid intake after experiencing reward downshift,
suggesting that just performing the licking response was not suffi-
cient to reduce negative affect (see comparable results but on the
lack of positive consequences for just licking in Ruiz et al., 2016).
The lack of impact of the sucrose downshift manipulation on wheel
running (a response also known to have reinforcing properties; e.g.,
Belke & Pierce, 2016) also makes this interpretation unlikely.
The present results are in accordance with studies showing
increased voluntary alcohol consumption and preference in non-
human animals exposed to a variety of aversive stimuli, including
uncontrollable foot shocks, physical restraint, forced swimming,
social isolation, social defeat and odor predator, among others
(e.g., Anderson et al., 2016;Anisman & Waller, 1974;Lynch et al.,
1999;Manjoch et al., 2016;Nash & Maickel, 1985;Newman et al.,
2018;Thompson et al., 2020;Wolffgramm, 1990). Reported dat a are
also concordant with human studies showing increased alcohol use
and abuse in patients with psychiatric pathologies, healthy subjects
exposed to a variety of negative events, and alcohol-dependent
subjects experiencing withdrawal (e.g., Anderson et al., 2016;
Becker et al., 2011;Briand & Blendy, 2010;Gil-Rivas &
McWhorter, 2013;Koob, 2014). Overall, these results have
been interpreted in terms of emotional self-medication, suggesting
that the anxiolytic effects of alcohol reduce negative affect and
provide a source of reinforcement for drug intake behavior (Blume
et al., 2000;Hall & Queener, 2007;Khantzian, 2013).
The most important result obtained in the present study refers to
the abolishing effect of voluntary wheel running on augmented
alcohol intake and preference induced by reward downshift: Animals
with simultaneous access to alcohol and a wheel for running did not
show increased alcohol intake after experiencing reward downshift, a
result that cannot be explained on the basis of response (fluid intake
vs. running) competition (see the absence of negative correlations
between alcohol intake and wheel turns in the Results section). The
reduction in sucrose concentration during the postshift phase was not
accompanied by changes in alcohol consumption or preference
provided rats could ran in a wheel, which increased slightly across
sessions. The absence of changes in alcohol intake from preshift to
postshift phases reveals that its potential reinforcing effect was not
substituted by the alternative running reinforcer.
There is extensive evidence showing the usefulness of physical
activity as an effective treatment for drug (including alcohol) use
disorders (Cabé et al., 2021;Georgakouli et al., 2017;Jensen et al.,
2019;Roessler, 2010;Weinstock et al., 2017). In line with these
clinical results, simultaneous access to a wheel for exercising
significantly reduces alcohol consumption and preference and
modifies alcohol drinking patterns in rodents (Darlington et al.,
2016;Ehringer et al., 2009;Hammer et al., 2010;McMillan et al.,
1995;Ozburn et al., 2008), albeit null and opposite results have also
been reported (Crews et al., 2004;Werme et al., 2002). However,
only a few studies have analyzed the extent to which physical
activity influences alcohol consumption induced by aversive/stress-
ful stimuli. In one such study (Reguilón et al., 2020), mice received
four sessions of repeated social defeat and 1 hr of access to a running
wheel three times per week. Once this phase concluded, animals
were trained in an operant alcohol (6%) self-administration proce-
dure. Social defeat increased motivation to obtain alcohol and
alcohol intake, an effect that was reversed by previous voluntary
wheel running.
Although the mechanisms underlying the impact of physical exer-
cise on drug use and abuse remain unclear (Lynch et al., 2013), the fact
that exercise activates the dopaminergic brain reward system suggests
that physical activity could serve as an effective hedonic substitute
to drugs, promoting the normal functioning of the brain reward and
antireward systems (Abrantes & Blevins, 2019;Darlington et al., 2016;
Ozburn et al., 2008). According to this view, intense exercise has
been shown to decrease alcohol craving in recovering alcoholics
(Ussher et al., 2004). Similarly, previous access to voluntary exercise
reduces anxiety-like behavior in rats, whereas withdrawal from
exercise access enhances alcohol intake (Lynch et al., 2019).
In the present study, reward downshift increased alcohol intake
without affecting wheel running, whereas wheel running abolished
the effect of reward downshift on alcohol consumption. These
results suggest that although wheel running was not an effective
alternative reinforcer to alcohol intake, its ameliorating effects on
negative affect (see Abrantes et al., 2019) could contribute to reduce
alcohol intake after experiencing reward loss. In accordance to this,
animals exposed to a frustrative reward omission task showed lower
hormonal and behavioral signs of anxiety when they had previous
exercise training in comparison with controls (Taylor et al., 2019).
Whether or not the present data can be interpreted in terms of
hedonic substitution will have to be addressed in future studies to
determine the usefulness of physical exercise to prevent the mal-
adaptive effects of frustration on drug use.
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Received December 22, 2021
Revision received April 16, 2022
Accepted May 23, 2022 ▪
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10 CASTEJÓN, FUENTES-VERDUGO, PELLÓN, AND TORRES
