The proposal maintains the rationale that the significance of intracranial self-stimulation (ICSS) lies in the anatomical and pharmacological systems responsible for the behavior. Research has followed 3-phase systematic approach: 1) Maps of ICSS sites from specific brain regions have been obtained; 2) Neuroanatomical tracing methods have been used to identify each of the neural elements in the vicinity of the ICSS sites. (Examples of such methods are: agglutin-horseradish peroxidase histochemistry, silver impregnation, and histochemical fluorescence.); and 3) Selective lesions have been made of systems, identified in the anatomical studies, and thought to be related to ICSS from a given brain region. The injection neurotoxins such as 6-hydroxydopamine or kainic acid directly at the site of ICSS has been particularly useful in this regard. This was accomplished by means of a combined electrode-cannula system. The present proposal will pursue those aspects of the project that seem most promising. One example of this is the need to define the role of the thalamus in brain reward mechanisms, in view of its newly described ability to support ICSS in certain of its regions, previously thought to be related stictly to sensory relay functions. There is also the need to assess the role of crossed and bilateral, as well as descending connections of ICSS areas. Finally, the use of the electrode-cannula will be continued and expanded, employing both tracing and lesioning methods. Each line of the proposed research stems directly from the systematic approach contained in this proposal, testifying to its ability to generate cogent data and point to new avenues of investigation. The approach offers the best opportunity to answer the most basic question about brain reward mechanisms: """"""""Does the brain operate with a single common underlying reward system, or are there multiple reward systems in the brain, each with its unique anatomical and pharmacological substrates as well as functional significance?""""""""
