We propose to extend substantially our investigations into the manner by which hallucinogens and opiates later sensory, associative and motor processes by seeking to determine their effects upon temporal, motivational, associative memory and complex stimulus processing. Our long-term objectives are to employ our detailed knowledge of the effects of abused drugs upon one or more of these processes in a search for common mechanisms as well as a basis for detailing a reinforcement and liability account of their abuse. The paradigms to be used will involve classical defense conditioning of the rabbit's nictitating membrane response (NMR) and classical reward conditioning of the rabbit's jaw movement response (JMR). Their status as model systems for the study of associative learning and drug action lie in their ability to: (a) exactly specify the stimulus conditions governing acquisition (and other learning) processes; (b) delineate the associative learning effects of the variables of interest from their effects on nonassociative, sensory and motor processes; (c) reveal sensitivity to incremental and decremental effects of drugs on learned behavior; (d) localize drug effects on learned behavior to sensory, associative and motor processes; and (e) allow the further partitioning of the three component processes of drug action to temporal, motivational, associative memory and complex stimulus processing. We are interested in comparing the effects of hallucinogens and opiates on these processes and in determining common effects and differences not shared by inactive compounds. Furthermore, we will examine the occurrence of tolerance and cross-tolerance on selected behavioral processes. In addition, by means of electrical stimulation of the pars oralis of the trigeminal sensory and the accessory abducens motor nucleus of the NMR, we propose to determine whether any observed effects upon motor processes can be further localized to the presynaptic sensory input or postsynaptic motor output of the NMR. Our studies are expected to provide the most complete characterization of the major effects of widely abused hallucinogens and opiates on behavioral processes implicated in subjective accounts of their effects. Accordingly, they may provide objective data for determining the basis of their abuse by humans. Animal models that detect effects of drugs of abuse over a range of behavioral processes would also provide a powerful model system for screening new drugs for their potential for abuse.
