A Tale of Two Addiction Theories: the effects of cocaine exposure on cue-induced motivation and action control

Cocaine addiction affects approximately 1.4 million Americans, costing the government billions of dollars and the addicted individual their life. Addiction is characterized by a continued desire to use a drug despite decreased enjoyment from taking it and a desire to abstain. Multiple theories attempt to explain how prolonged drug use induces the chronic brain changes that result in addiction. The incentive sensitization theory suggests that repeated exposure to drugs of abuse alters the neural circuitry that is involved in incentive motivation, the process that allows drugs and their associated stimuli to more strongly encourage drug-seeking behavior. Alternatively, the habit learning theory suggests that drugs of abuse pathologically subvert the reward-learning circuitry, leading to compulsive drug seeking triggered by drug-associated stimuli. Since both theories are based on the idea that drugs of abuse affect the dopaminergic system and alter normal reward processing, it has been proposed that drug exposure may also affect behavior for natural rewards. To understand the mechanisms by which cocaine use modifies reward-seeking behaviors, I have conducted experiments to investigate both addiction theories using cocaine and food rewards as the outcome. I have found that cocaine-paired cues promote cocaine-seeking and taking actions via a Pavlovian motivational mechanism. I have also explored the importance of the contingency of drug delivery and found that cocaine has a general effect on incentive motivation, with both self-administered and experimenter-delivered cocaine enhancing the ability of food-paired cues to motivate food-seeking behavior. This result was not obtained with animals that passively received cocaine infusions, suggesting a role of predictability in the effects of cocaine on incentive motivation. I have also found support for the habit learning theory, demonstrating that cocaine treatment can encourage habitual control of action selection for food rewards, even when feedback is given. However, experimenter-delivered cocaine does not prevent animals from learning to perform a behavior in a goal-directed fashion. Our results lend support to both theories, suggesting that drug induced changes to the dopaminergic systems may be affecting both incentive motivation and reward learning. These results have important implications for our comprehension of the neural processes involved in addiction