1. Effects of Environmental Enrichment on the Context Dependency
of Cocaine-Cue Extinction Learning for Relapse Prevention
• Cocaine addiction currently has no effective treatment
methods.
• Drug cue-extinction (exposure therapy) has been
proposed as a potential treatment method, but has
shown to be context dependent (Conklin & Tiffany et al 2002).
• To be of use in clinical settings, this treatment method
would need to be effective in a novel context.
• Previous studies show that context dependency of
extinction learning is overcome with administration of a
cognitive enhancing drug (e.g. DCS) (Torregrossa et al 2010).
• EE is equally effective as a cognitive enhancing drug
when brief interventions of EE are paired with cocaine-
cue extinction training (Gauthier et al 2015).
• EE enhances neurogenesis and cognitive functioning,
which in turn facilitates learning (Beauquis et al 2010; Fan et al
2007; Gauthier et al 2015).
• The context dependency of extinction learning may be
overcome if it is paired with EE.
• What effects does EE have on extinction learning and
relapse when extinction is given in a novel context?
• Beauquis, J., Roig, P., De Nicola, A. F., & Saravia, F. (2010). Short-Term
Environmental Enrichment Enhances Adult Neurogenesis, Vascular Network and
Dendritic Complexity in the Hippocampus of Type 1 Diabetic Mice. PLoS ONE,
5(11), e13993.
• Conklin CA, Tiffany ST. (2002). Applying extinction research and theory to cue-
exposure addiction treatments. Addiction, 97:155–167.
• Fan, Y., Liu, Z., Weinstein, P. R., Fike, J. R. and Liu, J. (2007), Environmental
enrichment enhances neurogenesis and improves functional outcome after cranial
irradiation. European Journal of Neuroscience, 25: 38–46.
• Gauthier, J. M., Lin, A., Nic Dhonnchadha, B. Á., Spealman, R. D., Man, H.-Y., and
Kantak, K. M. (2015) Environmental enrichment facilitates cocaine-cue extinction,
deters reacquisition of cocaine self-administration and alters AMPAR GluA1
expression and phosphorylation. Addiction Biology.
• Torregrossa, M. M., Sanchez, H., & Taylor, J. R. (2010). D-cycloserine Reduces the
Context- Specificity of Pavlovian Extinction of Cocaine Cues Through Actions in the
Nucleus Accumbens. The Journal of Neuroscience, 30(31), 10526–10533.
METHODS
• Cocaine self-administration
(0.3mg/kg) under a Second-
Order Schedule
• Adult Male Wistar rats, group
sizes varied n = 8-12
• Rats were placed into 1 of 3
groups:
• Group 1: Rats received EXT in
same drug context (A) with
no EE (control group)
• Group 2: Rats received EXT in
same drug context (A) with EE
• Group 3: Rats received EXT in
novel context (B) with EE
INTRODUCTION
RESEARCH QUESTION
During baseline self-administration (before treatments), there were no preexisting group differences
• One way ANOVAs confirmed this for average active (p=0.072) and inactive (p=0.28) lever responses,
and cocaine infusions (p=0.21).
• One outlier rat (†) disproportionately represented the ABA + EE group for inactive lever responses;
removing the outlier resulted in a more accurate representation of the group.
EE facilitated extinction learning
• During extinction (no cocaine delivery), lever pressing
generally decreased across weekly sessions.
• A two-way RM ANOVA showed a main effect of group
(F[2,25] = 4.1, p=0.030). Tukey tests show that the
rats receiving extinction in context A with EE
responded significantly less than the control group
(^ p=0.04).
• Dunnett tests showed that rats receiving EE had
significantly less responding than the control group
on extinction session 2, regardless if they received
extinction in context A or B (* p < 0.01).
RESULTS (CONT.)
EE deterred relapse after extinction in context A
• Repeated two-way ANOVA showed that there is
a main effect of group (F[2,25] = 7.61, p=0.003).
• Tukey tests showed that rats receiving extinction
in context A with EE responded significantly less
during reacquisition compared to rats receiving
extinction in novel context B with EE (^ p=0.002)
• Dunnett post-hoc tests showed that rats
receiving extinction in context A with EE
deterred cocaine relapse for up to 12 sessions
compared to the control group (* p<0.05).
CITATIONS
CONCLUSIONS
Presented by:
Kyle Mabry
• EE facilitated the rate of extinction learning, regardless of the change in context.
• Combining EE with extinction learning in context A deterred relapse to baseline
rates of cocaine self-administration.
• When EE was paired with extinction learning in context B, however, rats relapsed
immediately, as also observed in the control group.
• This suggests that EE is not able to overcome the context dependency of extinction
learning.
• Pairing EE with a cognitive enhancing drug may be able to surmount the context
dependency of extinction learning.
OR
Aspen bedding Aspen beddingAspen bedding Cedar bedding
= Intermittent tone
Black wall
Cedar bedding
= White noise
Clear wall
Aspen bedding
ABSTRACT
Addiction is marked by repeated cycles of abstinence followed by drug relapse
brought on by re-exposure to drug-paired cues. Extinction learning disassociates
drug-paired cues from the drug itself, but is context-dependent. We used
environmental enrichment (EE) paired with cocaine-cue extinction training to
investigate whether EE can overcome the context dependency of extinction
learning. Adult male rats were conditioned under a second-order schedule of
cocaine delivery and cue presentation. After establishing baseline rates of
cocaine self-administration, saline was substituted for cocaine during three
weekly extinction sessions. The first group (control group) was conditioned,
extinguished and tested for relapse in the same context (AAA design), but did
not receive EE. The second group was treated identically (AAA design), but also
received EE during extinction. The third group was conditioned and relapse
tested in context A, but extinguished with EE in a novel context (ABA design). EE
consisted of two 4-hr periods provided 24 hours before and immediately
following each weekly extinction session. One week later, cocaine was again
available for 15 daily self-administration sessions to study relapse in context A.
Results showed that EE facilitated rates of extinction learning, whether
conducted in context A or context B. As previously observed, combining EE with
extinction in context A inhibited cocaine relapse. However, when EE was
combined with extinction in context B, rats relapsed immediately, as observed
in the control group. Thus, EE cannot overcome the context dependency of
extinction learning. Adjunct drug therapies may be required to surmount this
obstacle in clinical settings.
RESULTS
†
PI: Kathleen M. Kantak
GS: Jamie Gauthier
EE was provided in 4-hr
blocks 24 hours before
and immediately after
each weekly extinction
session.
Baseline Cocaine Self-Administration
A B
A
B