RHODES, Justin/S; CRABBE, John/C; Oregon Health & Science Univ: The neural basis of motivation for natural and drug rewards

Motivation controls voluntary behavior up to the limit of physical capacity. Thus, it probably accounts for a large proportion of variation in behavior among individuals and species. Drugs of abuse can elicit powerful shifts in motivation and thus can provide a useful model. For example, when rats are placed into an environment where they had previously experienced a drug, the state of high motivation is associated with activation of specific brain regions, as indexed by levels of c-Fos protein. Here we develop a mouse version with methamphetamine (METH) for future use in comparing to models where food or a shock is substituted for METH. Male outbred mice were randomly assigned to two groups: “METH-paired” or “SAL-paired.” METH-paired subjects were injected with METH (2 mg/kg, ip) and then placed into an activity monitor where locomotor activity was measured for 30 min. After the test, the subjects were returned to their home cages where they were injected with saline (SAL) 90 min later. SAL-paired subjects were exposed to the identical procedure except the order of administration was reversed (i.e. they received SAL before being placed into the activity monitor and METH later in the home cage). This procedure was repeated on 10 consecutive days. On the test day, 48 hours after the final training session, all mice were given SAL and then placed into the activity monitors for 90 min. Immediately following the test session, the mice were sacrificed and their brains processed for immunohistochemical detection of c-Fos. Levels of c-Fos were correlated with locomotor activity among individuals in nearly every brain region examined but this did not account for large differences between SAL-paired and METH-paired mice in several key regions. Future plans are discussed to identify the specificity of the model. Supported by AA10270, AA07468 and a grant from the Department of Veterans Affairs.