| Conditioned Place Preference (CPP) is a behavioral measure of learning and reward widely used in studies of addiction. CPP is generally measured as the cumulative time an animal spends in a location previously paired with reward. However, this measure masks the different behavioral strategies that an animal could use. To discover the specific behavioral change underlying CPP, we used continuous video tracking of animals before and after morphine CPP training. Using a three room apparatus we analyzed room visit frequency and duration, and room transition profiles. We discovered that the rats have two distinct room transition profiles, simple and complex, that correspond to the rat's intended destination, suggesting that room transitions are discrete, location-directed actions. A computational model that included location-directed room transitions revealed an effect of conditioning on morphine room behavior. Specifically, conditioning increased the probability of direct saline to morphine room transitions. Therefore, the expression of CPP is explained by an increase in the probability of spontaneous location-directed transitions into the morphine room. Nucleus Accumbens (NAc) neurons are required for the expression of CPP. To determine how they contribute we recorded their activity during CPP testing. During test sessions, when the rats freely explored all rooms, 26% of neurons were preferentially excited or inhibited while in one of the three rooms. Most of these neurons also showed transient responses during room transitions. Some room transition responses were selective for transitions in only one direction or to a particular room. Prior to conditioning, approximately equal populations of NAc neurons encoded excitations or inhibitions to each room (morphine paired, center or saline paired). Conditioning increased two of these populations, those inhibited while the rat was in the morphine room and those excited in the saline room. Thus, the increase in proportion of NAc neurons that code for excitation in the saline room and inhibition in the morphine room correlate with the observed behavioral bias to exit the saline room toward the morphine room during expression of morphine CPP. These results suggest a potential mechanism by which activity in NAc neurons could lead to increased time in the morphine paired room. |
