Stimulant abuse may engender explosive and seemingly unpredictable violent outbursts in certain individuals, whereas others withdraw entirely from social interactions.
The specific aims of the proposed research are as follows: 1. How functionally specific or pervasive are the behavioral tolerance, sensitization and potentiation phenomena in the profile of opiate and psychomotor stimulant effects after distinctive experiences in situations of social conflict and affiliative behavior? 2. How do experience with certain social behaviors modulate the symptoms of opiate withdrawal? Which are the catecholaminergic mechanisms that mediate heightened aggressive and defensive reactions during opiate withdrawal? 3. How do experience with reproductive and aggressive behavior that are based on the hormonal status of the individual, particularly in females, influence the behavioral and physiological effects of opiates and psychomotor stimulants? 4. Are individual differences in sensitivity to amphetamine's and cocaine's acute and chronic behavioral effects linked to distinctive social experiences? We plan to conduct studies that will (1) parametrically determine the minimal and """"""""optimal"""""""" social, aggressive, defensive and submissive behaviors that result in modulation of behavioral and physiological functions, (2) use biochemically identified selective ligands at different opiate receptor subtypes as well as dopaminergic and noradrenergic receptor subtypes as probes for functional assessments, and (3) quantitatively assess selected functions such as DA, DOPAC, NE, 5-HT, 5-HIAA in discrete fore- and midbrain regions, serum prolactin and corticosterone, telemetered heart rate, blood pressure, core temperature, pain and startle responses, motor activities, discriminative stimulus properties, maternal care behavior, sexual, social, aggressive, defensive, submissive and flight reactions. Additional experiments will investigate the effectiveness of acute morphine administration in comparison to incrementally longer morphine exposure to induce heightened aggressive behavior. Further experiments are designed to examine the receptor super- sensitivity proposal by challenging animals during opiate withdrawal with several selective dopaminergic and noradrenergic receptor agonists, first systemically, and subsequently by intra- cranial infusion into specific target regions. A final set of experiments will attempt to antagonize amphetamine and cocaine effects on social and aggressive behavior with prazosin and other drugs that interfere with noradrenergic and dopaminergic neurotransmission.
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