Project 0003 in the Center for Neurobiological Investigation of Drug Abuse will investigate the role of nucleus accumbens (NA) and other brain regions in the control of cocaine self-administration in non-human primates. These studies are designed explicitly to determine whether encoding of different phrases of the internal between drug infusions in the monkey provokes similar patterns of discharge in NA cells as demonstrated in the rat-self administration model in the prior funding period of the Center. The extensions of those studies to the non-human primate provides for a more informative means of assessing and characterizing single and multi-neuron activity in several different brain regions simultaneously and under more complex circumstances of stimulus and context control than could be achieved in the rodent. Experiments are designed to determine what brain regions beside the NA are critically activated or inhibited in terms of single neuron firing changes, during cocaine self-administration and during assessment of potent cocaine analogs (tropanes) in similar paradigms. Candidate brain regions to be explored are those maximally affected by either acute cocaine injections or self-administration of cocaine as shown by imaging of 2-DG metabolic maps in monkeys. These include, NA (shell and core), dopaminergic cells in the ventral tegmental area (VTA), the amygdala (medial and basal), the hippocampus (CA1 and subiculum) the cingulate and orbital frontal cortex. These areas in most cases supply afferent projections to the NA in the monkey and therefore will be examined simultaneously with the NA for evidence of a functional underlying substrate. Further studies will be conducted to determine extent to which NA and other regional cell firing patterns are controlled by the associative properties of stimuli that have been paired with drug delivery. In particular studies will investigate whether the stimuli, or the contexts in which stimuli occur, are more relevant to the associations formed by pairing with drug versus appetitive reward. In addition when such associations are formed, are those stimuli paired with drug reinforcers more capable of modifying behavior outside the original reward context in comparison to non-drug related reinforcers. Such differential reinforcing capacity should be reflected as differential cell firing patterns in the implicated brain regions, providing further insight into how drugs like cocaine affect motivational processes and gain control over behavior.