- Individual rats exhibited variability in voluntarily consuming ethanol in their home cage. Rats that drank more ethanol in their home cage were more likely to work to obtain ethanol rewards in an operant conditioning task. - In the operant conditioning task, all rats preferred sucrose rewards to ethanol rewards as demonstrated by their faster response times and retrieval of more sucrose rewards compared to ethanol rewards. However, rats would still perform the task to obtain ethanol rewards when sucrose was also a possible reward. - Future studies will analyze neural activity in the medial and lateral orbitofrontal cortex in response to cues predicting ethanol or sucrose rewards and how previous reward trials impact neural activity and reward-seeking behavior.

1. HOME CAGE CONSUMPTION OF 20% ETHANOL PREDICTS REWARD SEEKING BEHAVIOR
INTRODUCTION
Alcohol
• 3rd preventable cause of death in the US [5]
• In 2010, economic costs of excessive alcohol consumption was $249 billion [2]
• Individual preference for alcohol is predictive of alcohol use disorder [7]
Orbitofrontal Cortex
• Influential in motivation, predicting reward, and relapse in addicts [3, 4, 6]
• Regional differences in neuronal firing in the medial and lateral OFC (mOFC and lOFC) [1, 4]
There are very few studies examining the role of the mOFC and lOFC in alcohol seeking.
Siegal, R.E., Hernandez, J.S. and Moorman, D. E.
Psychological and Brain Sciences, Neuroscience and Behavior Program, University of Massachusetts Amherst
OPERANT TASK BEHAVIORAL DATA
Reward
and end
of trial
Longer
than
500 ms
= Long
nose
poke
Tone
signals
type of
reward
Shorter
than
100 ms
= Short
nose
poke
Start of
Trial
House
light
turns off
Nose
poke for
100 ms
1, 5 or
10 kHz
tone
Exit nose
poke in
500 ms
Reward
delivered
METHODS
Figure 3. Intermittent Access to 20% Ethanol
A.
A.
Figure 7. Individual variability in home cage drinking
Figure 10. There was a significant difference in number and percent of rewards earned between sessions
Figure 8. There was a significant difference in licking behavior between sessions
HOMECAGE IA TO 20% ETHANOL
Figure 11. There was a significant difference in number and percent of rewards retrieved between sessions.
Figure 2. Procedure Overview
A.
Rats initiated significantly more trials and
triggered significantly more tones in
sessions containing sucrose rewards (Fig.
9A and 9B; *p < 0.05, **p < 0.01, ***p <
0.001, ****p < 0.0001).
B.
Summary
• Individual rats expressed variability in home cage ethanol consumption
• Individual preference for ethanol may be a predictor of future ethanol seeking behavior in rats
• Rats prefer sucrose over ethanol rewards; however rats will risk receiving ethanol rewards when there is a possibility
that they may receive a sucrose reward instead
Future Directions
• Analyze the neural activity in the mOFC and lOFC when presented with cues predicting ethanol or sucrose rewards
• Analyze the effect of previous ethanol or sucrose trials in interwoven sessions
SUMMARY and FUTURE DIRECTIONS
1. Burton, A. C., Kashtelyan, V., Bryden, D. W., & Roesch, M. R. (November 07, 2013). Increased Firing to Cues That Predict Low-Value Reward in the Medial Orbitofrontal Cortex. Cerebral Cortex, 24, 12, 3310-3321.
2. http://www.cdc.gov/alcohol/fact-sheets/alcohol-use.htm
3. Koob, G. F., & Volkow, N. D. (March 01, 2010). Neurocircuitry of Addiction. Neuropsychopharmacology, 35, 4.)
4. Moorman, D. E., & Aston-Jones, G. (January 01, 2014). Orbitofrontal cortical neurons encode expectation-driven initiation of reward-seeking. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 34, 31,
10234-46.
5. National Institute on Alcohol Abuse and Alcoholism. Alcohol Facts and Statistics. (n.d.). Retrieved December 19, 2015, fromhttp://www.niaaa.nih.gov/alcohol-health/overviewalcohol-consumption/alcohol-facts-and-statistics
6. Schoenbaum, G., Roesch, M. R., Stalnaker, T. A., & Takahashi, Y. K. (January 01, 2009). A new perspective on the role of the orbitofrontal cortex in adaptive behaviour. Nature Reviews. Neuroscience, 10, 12, 885-92.
7. Spoelder, M., Hesseling, P., Baars, A. M., Lozeman-van, . K. J. G., Rotte, M. D., Vanderschuren, L. J. M. J., & Lesscher, H. M. B. (December 01, 2015). Individual Variation in Alcohol Intake Predicts Reinforcement, Motivation, and
Compulsive Alcohol Use in Rats. Alcoholism: Clinical and Experimental Research, 39, 12, 2427-2437.
8. Verschure, P. F. M. J., Verschure, P. F. M. J., Pennartz, C. M. A., & Pezzulo, G. (January 01, 2014). The why, what, where, when and how of goal-directed choice: Neuronal and computational principles. Philosophical Transactions of the
Royal Society B: Biological Sciences, 369, 1655.)
9. Mormede, P., Colas, A., & Jones, B. C. (January 01, 2004). High ethanol preferring rats fail to show dependence following short- or long-term ethanol exposure. Alcohol and Alcoholism (oxford, Oxfordshire), 39, 3.)
Thank you to Jessica Feliciano, Aidan Leith, Kathy Tran and Kerrin Bersani. A special thank you to John Hernandez for figures 3A, 4A and 6A, but more importantly for his guidance throughout
my undergraduate research. Thank you to Dr. Moorman for his mentorship and support. Thank you to the Commonwealth Honors College at the University of Massachusetts Amherst for their
financial contributions.
ACKNOWLEDGEMENTS
Figure 1. Hypotheses
A.
HOME CAGE
INTERMITTENT
ACCESS TO ETHANOL
Figure 3A
• 40 ml 20% ethanol
3x/week TRAINING
• 40 ml water 2x/week
• 4 weeks
TRAINING
Figure 4A
• 15% sucrose
solution
• 85% reward
retrieval
SURGERY
• 32 electrodes
(16 in mOFC
16 in lOFC)
• A/P: 3.6-4.6 mm
D/V: -5.0-5.2 mm
TESTING
Figure 5A and 5B
• Electrophysiology
recordings
• Operant task with
reward
HISTOLOGY
Figure 6A
• Perfuse
rats
• Stain brain
slices (40
um)
Figure 4. Operant Box Setup
Figure 5. Operant Task
Figure 6. Recording sites
A.
A.
C. Low, medium and high drinkers
Figure 14. There was a significant difference in the time taken to retrieve the reward during sucrose and ethanol trials
References
OFC Activity
for Ethanol
Ethanol
Predicting
Cue
Sucrose
Predicting
Cue
Home Cage
Ethanol
Consumption
Rats
High
Drinkers
Reward
Seeking
Reward
Seeking
more mOFC
less lOFC
Low
Drinkers
Reward
Seeking
No Reward
Seeking
less mOFC
more lOFC
A.
Rewards
earned: All
trials
B.
Rewards
earned :
Sucrose,
10% and
20%
ethanol
C.
Rewards
retrieved:
All trials
D.
Rewards
retrieved:
Sucrose,
10% and
20%
ethanol
These graphs suggest that although not significant, rats with high levels of home cage drinking tend to earn and retrieve more
sucrose and ethanol rewards (Fig. 15A, 15B, 15C and 15D; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001*).
Figure 9. There was a significant difference in number of initiated trials and tones played between sessions
Figure 12. Home cage drinking predicts future ethanol seeking behavior
These graphs suggest that home
cage drinking is an indicator of
future ethanol consumption
(Fig. 12A and 12B; *p < 0.05).
B. Home cage drinking and rewards retrieved
A. Total initiated trials: All sessions B. Total tones played: All sessions
A. Licking behavior: Blocked sucrose
and ethanol sessions
B. Licking behavior: Interleaved sucrose
and ethanol sessions
C. Licking behavior: Interleaved
ethanol sessions
Rats licked significantly more for sucrose when compared to ethanol (Fig. 8A, 8B, and 8C; *p < 0.05, **p < 0.01, ***p < 0.001,
****p < 0.0001).
A. Total rewards retrieved: All sessions
C. Percent of rewards retrieved:
blocked sucrose and ethanol sessions
Average home cage drinking increased from 2.68 g/kg on day 1 to 4.18 g/kg on day 13 (Fig. 7A). Individual variability was
seen in rats’ home cage drinking (Fig. 7B). Rats were split into low, medium and high drinkers based on previous
determinants of high drinkers (Fig. 7C)
B.
A. House light off to initial nose
poke: All sessions
B. Tone off to leave nose poke:
Blocked sucrose and ethanol sessions
C. Tone off to leave nose poke: Interleaved
sucrose and ethanol sessions
Rats were significantly faster at initiating trials during session containing sucrose rewards (Fig. 13A; *p < 0.05, **p < 0.01, ***p <
0.001, ****p < 0.0001). Rats were also significantly faster at leaving the nose poke to retrieving the reward during interleaved
sucrose and 10% ethanol sessions (Fig. 13B and 13C; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).
A. Time taken to retrieve the reward: Blocked sucrose and
ethanol sessions
B. Time taken to retrieve the reward: Interleaved sucrose and
ethanol sessions
Rats were significantly faster at retrieving sucrose rewards compared to an ethanol rewards (Fig. 14A and 14B; *p < 0.05, **p < 0.01,
***p < 0.001, ****p < 0.0001).
Figure 15. Rewards earned and retrieved for low, medium and high drinkers
A. Home cage drinking and licking behavior
Figure 13. There was a significant difference in the time taken to initiate trials and to leave the nose poke during
blocked and interwoven sucrose and ethanol trials
B. Home cage drinking by animalA. Home cage drinking by day
*r = 0.58
B. Total rewards retrieved: Interleaved sucrose and
ethanol sessions
D. Percent of rewards retrieved: Interleaved sucrose and
ethanol sessions
Rats retrieved significantly more rewards in sessions where sucrose was a possible reward (Fig. 11A, and 11B; *p < 0.05, **p <
0.01, ***p < 0.001, ****p < 0.0001). The percent of rewards retrieved (of rewards earned) was significantly higher for blocked
sucrose sessions (Fig. 11C and 11D; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).
A. Total rewards earned: All sessions B. Total rewards earned: Interleaved sucrose and ethanol
sessions
C. Percent of rewards earned: blocked
sucrose and ethanol sessions
D. Percent of rewards earned: Interleaved sucrose and
ethanol sessions
Rats earned significantly more rewards in sessions where sucrose was a possible reward (Fig. 10A, and 10B; *p < 0.05, **p <
0.01, ***p < 0.001, ****p < 0.0001). The percent of rewards earned (of tones played) was significantly higher for blocked
sucrose sessions (Fig. 10C and 10D; *p < 0.05, **p < 0.01, ***p < 0.001, ****p < 0.0001).