1. Microinjection of dopamine antagonists into the nucleus accumbens core
reduces high effort choices during decision making
Maria Shibatsuji, Sara E. Morrison, Saleem Nicola
Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY 10461
1. Nicola, S.M. The flexible approach hypothesis: unification of effort and
cue- responding hypotheses for the role of nucleus accumbens dopamine
in the activation of reward- seeking behavior. J Neurosci 30, 16585-16600
(2010).
2. Salamone, J.D., Correa, M., Farrar, A. & Mingote, S.M. Effort- related
functions of nucleus accumbens dopamine and associated forebrain
circuits. Psychopharmacology 191, 461- 482 (2007).
3. Walton, M.E., et al. Comparing the role of the anterior cingulate cortex
and 6- hydroxydopamine nucleus accumbens lesions on operant effort-
based decision making. Eur J Neurosci 29, 1678-1691 (2009).
Methods References
Results & Discussion
• Our preliminary results suggest that microinjection of dopamine
antagonists into the NAc core increased rats’ choices of the low
effort / low reward arm on both tasks.
• In the one barrier task, the D1 antagonist and a high dose of the
D2 antagonist decreased high-effort/high-reward choices.
• In the two barrier task, a high dose of the D2 antagonist
decreased high-effort/high-reward choices.
• High doses of the D1 antagonist also increased omitted trials in
several rats (data not shown).
• These results suggest that D2 receptor activation in the nucleus
accumbens might be specifically important for the exertion of
effort to obtain larger rewards. D1 receptor activation, on the
other hand, might be involved more generally in goal-directed
behavior.
Acknowledgements
Studies have suggested that animals conduct cost-benefit analyses in
order to determine if an increased amount of work or risk is worth
undertaking for a higher reward. Dopamine released in the core of
nucleus accumbens (NAc) is thought to play a role in effort-based
decision making by regulating the amount of effort invested for a reward.
While it is established that NAc dopamine is needed to perform high
effort tasks, the underlying neural mechanisms of effort-based decision
making are up for debate.
One hypothesis is that the activation of dopamine receptors directly
influences effort-related decision making (Salamone et al., 2007): the
activation of dopamine receptors allows animals to overcome response
constraints that may prevent them from engaging in high effort tasks.
However, other studies suggest that the effort exerted in order to obtain
reward is not affected by NAc dopamine manipulation (e.g. Walton et al.,
2009), implying that NAc dopamine might not play a specific role in
supporting effort. Instead, we hypothesized that NAc might play a more
general role in goal-directed behavior. In order to test these hypotheses,
high vs low effort preferences were measured using a T-maze after
microinjecting with one of two dopamine antagonists or saline.
Introduction
Financial support was provided by the Summer Undergraduate Research
Program (SURP). We would like to thank David Novy, Ashley Wright, Cindy
Reyes, James Kim, Kevin Caref, and Mo-87 – Mo-94.
Time course of training and experiment
Rat completing 2 vs 1 barrier training
. Paxinos & Watson 2007
During training, rats developed a
preference for the high-effort/high-
reward arm of the T maze
Habituation
4-5 days
Discrimination
Training
7-9 days
1 barrier training
4-6 days
High barrier training
7-9 days
High barrier with
platform training
4-5 days
2 vs 1 barrier
training
4-7 days
Surgery
7 days
Recovery
5-7 days
Microinjections
14 days, every other
day
• Subjects were 8 male rats
• Rats were trained on a T-maze baited
with a large reward (3 sucrose pellets)
in one arm and a small reward (1
pellet) in the other
• Half of the rats were presented with
one barrier in the HR arm and no
barrier in the LR arm (“one-barrier
task”)
• The other half of the rats were
presented with two barriers in the HR
arm and one barrier in the LR arm
(“two-barrier task”)
• Cannula implantation surgery:
Bilateral cannulae were placed into the
NAc core (coordinates in mm relative
to bregma: AP +1.2, ML ± 2) using
standard aseptic procedures
• Prior to being placed in the T-maze,
rats were microinjected in the NAc
core with either a dopamine D1
receptor antagonist (SCH 23390;
“Schering”) or a D2 receptor
antagonist (raclopride)
Vehicle SCH0.5 SCH1 SCH2
RAC1 RAC2 RAC4
%higheffortchoices
One-barrier task: D1 or D2 receptor
blockade reduces high effort choices
Location of cannula placement
%higheffortchoices
Vehicle SCH0.5 SCH1 SCH2
RAC1 RAC2 RAC4
Two-barrier task: D2 receptor
blockade reduces high effort choices
p < 0.1, t-test
p < 0.1, t-test
p < 0.05, t-test
*