The purpose of this proposal is to investigate the greater detail the deleterious effects of opiates on learning and sensory processing of stimuli. Classical (Pavlovian) conditioning of the rabbits nictitating membrane response will be employed because this paradigm allows one to accurately specify the behavioral processes and anatomical systems being affected by a drug. Thus, alterations in the acquisition of conditioned responses produced by a drug will be further analyzed in terms of the primary behavioral processes being affected. For example, 1) the effects of morphine on behavior associated with shock and air-puff aversive unconditioned stimuli will be compared to behavior associated with a water appetitive unconditioned stimulus, 2) possible alterations in the motivational value of aversive unconditioned stimuli by morphine will be investigated using a shock-escape task, and 3) the effects of morphine on the unconditioned excitatory effects of a tone on the reflex response will be investigated. Pharmacological analysis of drug effects will include: 1) dose-effect determinations for various agonist-antagonist functions using ethylketocyclazocine and morphine as agonists and naloxone, N-allynormetazocine and MR 2266 as antagonists, 2) examination of tolerance 3) the role of endogenous opioid systems through the use of intraventricular injections of various peptides (e.g., enkephalins, endorphins, and dynorphin), and 4) the role of the catecholamine systems in opiate effects. Finally, the anatomical locus of opiate effects on behavioral processes will be investigated through the use of te [14C]-2-deoxy-d-glucose technique for determination of localized changes in glucose utilization presumably related to changes in neuronal activity produced by a drug. The wide-spread use of opiates as analgesics and drugs of abuse necessitates the need for a clearer understanding of potential behavioral toxicity with their use.
