The proposed work systematically dissects the notorious link between stimulant abuse, violence and social stress in ethologically valid animal preparations integrating behavioral, physiological and neuro- pharmacological research strategies. The key feature of the current proposal is the characterization of individuals at the behavioral, physiological and neurochemical level in terms of their vulnerability to the aggression-heightening and stress-potentiating effects of psychomotor stimulants and opiates. One set of specific aims focusses on self- administered psychomotor stimulants and opiates and their link to aggressive and violent behavior as well as to social stress in terms of their behavioral and physiological determinants. A second set of specific aims focuses on the neuropharmacological mechanisms that mediate the increases and decreases in self-administered cocaine and opiates resulting from the exposure to aggressive behavior and social stress. Specifically, the first experimental series seeks to determine whether or not different types of aggressive, defensive, submissive and non- agonistic social behavior will differentially affect cocaine and morphine i.v. self-administration. Experimental protocols are designed to assess whether or not rats and squirrel monkeys displaying submissive behavior develop cross-sensitization with cocaine, and also potentiation and tolerance to morphine. A second experimental series investigates how psychomotor stimulants and opiates modulate vocal signals as quantifiable expressions of affective states in addition to their effects on postural displays in situations of social conflict. These experiments use pharmacological probes that target DA and opioid receptor subtypes in several discrete limbic and mesencephalic regions, in order to investigate the mechanisms for opiates' and psychomotor stimulants' profound disturbance of the communication processes. A third experimental series focuses on an individual's circadian rhythmicity of autonomic functions, as monitored continuously via biotelemetry senders, as well as on the response and adaptation to environmental and pharmacological challenges as potential predictive indices of psychomotor stimulant and opiate effects in situations of social conflict. The fourth experimental series focuses on a range of social """"""""stressors"""""""" in reproductive and agonistic contexts and examines with in vivo microdialysis common or discrete forebrain dopamine systems during """"""""social stress"""""""" and cocaine """"""""reward"""""""". Protocols are designed to investigate the release of dopamine and its metabolites during social stress or i.v. cocaine self-administration or both, and to investigate potentially protective treatments.
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