Because drug abuse implies that normally rewarding activities become devalued relative to supernormal drug rewards, an incentive relativity paradigm is proposed in which normally rewarding 4% sucrose solutions become excessively devalued following experience with """"""""supernormal,"""""""" 32% sucrose solutions. Incentive relativity develops in stages, including: representing the incentive object (pre-shift solution), strong habit formation, a potential for physical dependency on the substance, detection of the incentive shift and evaluation of the normally rewarding alternative, exaggerated appetitive responses related to the missing substance, the activation of a stress response when that substance is not found, and a gradual recovery process whereby the relatively unsatisfactory incentive (the post-shift solution) eventually becomes acceptable. We hypothesize that high corticosterone (B) mounts central stress networks that enhance learning, performance, and recovery from incentive relativity effects. We intend to manipulate chronic stress variables (e.g., deprivation, B, corticotropin-releasing factor (CRF), opioids) and measure behavioral and neuroendocrine variables relevant to the acquisition, performance and recovery processes in an incentive relativity paradigm. We will test 4 hypotheses: 1. incentive shifts modify stress circuitry mediating psychological stressors; 2. High B improves acquistion and performance of sucrose drinking prior to the shift, and drinking and instrumental performance after the shift; 3. High B (and/or food deprivation) intensifies incentive relativity effects on a maze; and, 4. CRF and opioid systems are critical central opponent modulators of chronic stress relevant to incentive relativity effects. Methods include: behavior, ad lib and restricted food intake, immunocytochemical labeling, and double-labeling of cells for immediate-early genes and CRF, GABA and opioid peptides, adrenalectomy with B replacement, infusions into the ventricle of CRF-, mu/delta-opioid receptor antagonists and kappa-opioid receptor antagonists, before and after the shift in sucrose solution. The results should reveal brain mechanisms involved in incentive relativity and responses engendered in a paradigm analogous to drug-taking behavior. Because drug addiction and stress-induced relapse to drug taking have major social and societal, psychological and economic costs, studies that reveal mechanisms associated with drug taking behavior are of direct relevance to human health and drug addiction.
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