The purpose of this research is to provide a foundation for understanding the inheritance of sensitivity to the effects of cocaine and other psychomotor stimulants. The basic hypothesis is that behavioral stimulants like cocaine, amphetamine and caffeine produce their effects by initially interacting with different biochemical systems. This is most clearly demonstrated by describing the separable effects of these drugs in inbred mice and their recombinant inbred lines. The proposed studies will examine the effects of cocaine, norcocaine, methylphenidate and d-amphetamine on mouse body temperature, spontaneous locomotor activity, operant behavior and drug discrimination tasks. Both the progenitor strains (e.g. C57BL/6, DBA/2J) and recombinant inbred lines (e.g. BXD-11, BXD21, etc) will be used to study the separable or associated inheritance of sensitivity to these drug effects. Chronic administration of each of the stimulants will be studied to determine the relationship between acute effects and the magnitude of tolerance or sensitization observed.
