Reference-dose method and cocaine-conditioned choice

DESCRIPTION (provided by applicant): Research supports the assumption that associative learning processes contribute to acquisition, maintenance, and/or relapse of habitual drug-taking patterns. One preclinical animal model that has contributed importantly to understanding these conditioned associations is the cocaine place-conditioning preparation in rats. In a "standard" place-conditioning experiment, one distinct environment is repeatedly paired with cocaine administration; a second environment is equally experienced without cocaine. In a later drug-free test, rats given free access to both environments will spend more time in the cocaine-paired environment indicating that the paired environment has acquired rewarding value that controls approach/drug-seeking behaviors. Unfortunately, this widely used method is relatively insensitive to such variables as changes in cocaine dose (i.e., conditioned preference tends to be all-or-none) thus limiting its usefulness for a more detailed examination of processes mediating drug-seeking behavior. The main goal of the research in this proposal is to systematically assess the utility of a modified version of the standard protocol that overcomes some of these limitations. This new method, termed "reference-dose procedure," provides a known cocaine conditioning history in both environments (cf. standard protocol only conditions one environment). The following Aims will be used to obtain this goal. Specific Aim 1 will assess the change in choice behavior that occurs when varying doses of cocaine paired with one environment (e.g., 0.1, 0.3, 0.45, 0.6, 0.9, or 1.2) compete with another environment paired with a moderate or low reference-dose of cocaine (i.e., establish dose-effect curves). Specific Aim 2 will determine the extent to which the reference-dose method increases the sensitivity of the place conditioning procedure to antagonism using the dopamine D1 receptor antagonist SCH-23390. This research will provide the requisite foundation for this more sensitive reference-dose method. In doing so, new research into basic cognitive, behavioral, and neurobiological processes mediating drug-conditioned choice behavior will become possible. That research could translate into more effective intervention strategies.