Associative learning, decision-making, and addiction

National Institute On Drug Abuse

Investigators

Linked publications & trials

Abstract

Addiction and other neuropsychiatric diseases involve altered learning and decision-making. The mechanism of these alterations, the circuits affected, and their significance to behavior are not well understood. We are using an animal models of addiction, associative learning and decision making to study the neural circuits mediating simple associative learning and decision-making and to identify critical changes that may underlie addiction and other co-morbid neuropsychiatric disorders. It is hoped that by better understanding these changes, we will have better models for intervention. In the current year, we have published several dozen papers addressing how neural circuits mediate associative learning and decision-making and how these processes are altered by use of addictive drugs. Several studies have linked processing in the orbitofrontal cortex to critical associate learning functions and in particular to the definition of task states based on hidden or partial external information. This work in both rats and humans better defines the orbitofrontal cortex' role in building mental models of the world, culminating with a novel proposal that this area serves as a "cartographer" in the construction of Tolman's cognitive maps. This past year we have also published data and presented new work showing that cocaine use in rats leads to a selective degradation and oversimplification of the maps due to changes in orbitofrontal processing. Ongoing work now is using D3 agents in an attempt to mitigate these deficits. We have also published papers implicating an orbitofrontal-dopaminergic circuit in latent inhibition in collaboration with Mel Sharpe at UCLA and Erin Calipari at Vanderbilt. These two papers show that dopamine signaling is necessary for learning to ignore cues, and that the OFC is likely necessary for the inferring the hidden state of "non-reward" that this learning is founded on. This work provides additional examples of how these two important regions work together to build models of the world. Finally the lab has done well on a practical basis: 2 postdocs have left for tenure-track faculty positions, 2 graduate students successfully defended their dissertations, we landed several external grants including two K99's and a collaborative r01, and published widely, including work in Nature, Neuron, and Nature Neuroscience among other places.