The functional significance of intratanial self-stimulation (less) is not fully understood. The proposed experiments are based on the view that the significance of ICSS is closely related to the anatomical systems that support this behavior. Past attempts to obtain a parsimonious explanation for the widespread occurrence of ICSS in the brain have focussed on central catecholaminergic (CA) systems as critical edicators. However, recent results have questioned the CA hypothesis; indeed, they point to certain non-CA systems as possible substrates of ICSS. Proposed studies will use ortho- and retrograde tracing methods to identify all of the neutral systems in the vicinity of specific ICSS sites. Thus identified, each system will be assessed for its contribution to that ICSS. Methods to be used in the identification aspect will include histochemical fluorescence, silver impregnation, horseradish peroxidase, and labelled protein autoradiography. Techniques applied to the assessment aspect will fall into two categories: selective lesions; or psychopharmacological treatment (or both). Where possible, lesions will be induced by intracerebral injections of specific neurotoxins; for example, 6-hydroxydopamine will be used in cases where the CA systems are being investigated. Pharmacological studies will assess the effects of psychoactive drugs on ICSS. The agents to be used will either enhance or block the nearptransmission properties of the particular system(s) under investigation. While all central ICSS loci may be considered as potential candidates for the proposed studies, principal experiments will concentrate on those loci in which preliminary evidence is available. Strong parallels have been drawn between the effectiveness of certain "mood-altering" drugs on affective disorders and on ICSS. It has also been hypothesized that ICSS is related to the rewarding properties of non-medically used drugs such as amphetamine and cocaine. It is hoped that the proposed research will eventually contribute to practical applications in those areas.