Psychopathological conditions in which decision making is impaired are
common and include schizophrenia, attention deficit hyperactivity disorder, and
addiction, among others. This dissertation aimed to investigate the role of cholinergic
signaling in risky and impulsive decision making. Rats were trained in either a
“probability discounting” task in which they chose between small guaranteed and large
probabilistically delivered food rewards (a measure of risky decision making), or a
“delay discounting” task in which they chose between small immediate and large
delayed food rewards (a measure of impulsive decision making). Rats were also divided
into high and low “risk-taking” or “impulsive” groups on the basis of their performance
in the tasks.
Experiments 1 and 2 examined the effects of cholinergic drugs on performance in
the probability and delay discounting task, respectively. In Experiment 1, acute
administration of the acetylcholinesterase inhibitor donepezil decreased choice of the
large risky reward in “risk-taking” rats. Acute administration of nicotine increased
choice of the large risky reward in both groups, whereas administration of the nicotinic receptor antagonist mecamylamine decreased choice of the large risky reward in “risktaking”
rats. In Experiment 2, nicotine increased choice of the large delayed reward and
mecamylamine shifted impulsive choice in a non-specific manner in “impulsive” rats.
The muscarinic receptor agonist oxotremorine decreased choice of the large delayed
reward in “non-impulsive” rats and increased choice in “impulsive” rats, while treatment
with the muscarinic receptor antagonist atropine increased impulsive choice in all rats.
In Experiment 3, another group of rats was used to examine correlations between
baseline performance in both discounting tasks and nicotinic receptor density levels in
several brain regions. Impulsive choice was positively correlated with α4β2 receptor
levels in ventral hippocampus and nucleus accumbens shell, and α7 receptor levels in the
basolateral amygdala, such that greater impulsivity was associated with higher receptor
levels. Additionally, risky choice was negatively correlated with α4β2 receptor levels in
nucleus accumbens shell, such that greater risk was associated with lower receptor
levels. These experiments suggest that cholinergic receptors are involved in cost-benefit
decision making and that they may prove a useful target for treatment of
psychopathological conditions in which decision-making deficits are present.
| Identifer | oai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2010-12-8765 |
| Date | 2010 December 1900 |
| Creators | Mendez, Ian Alfredo |
| Contributors | Setlow, Barry, Cepeda-Benito, Antonio |
| Source Sets | Texas A and M University |
| Language | en_US |
| Detected Language | English |
| Type | thesis, text |
| Format | application/pdf |
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