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Tho present thesis represents a summary or research done by the author (and others) that was conducted with heroin addicts and drug abusers undergoing behavioral and pharmacological therapy at Stockton State Hospital, Stockton, California. From June 1970 to December 1970 the Research Department of Stockton State Hospital, in conjunction with the Drug Abuse Program at Stockton State Hospital, conducted research investigating a number of difference facets relating to inpatient programs for heroin addicts undergoing methadone maintenance and drug abusers. These facets included the investigation and evaluation of (a) motivational factors; affecting the voluntary participation of inpatient heroin addicts and drug abusers in behavioral and pharmacological therapy, (b) the effectiveness of the synthetic narcotic methadone hydrocloride as a primary reinforcing technique for appropriate behavior, (c) the effectiveness of various therapeutic approaches used in conjunction with behavioral modification techniques, and (d) the effect of methadone on perceptual and motor functioning in the heroin addict under-going methadone maintenance. The present thesis is a compilation cf these research projects.

Indiana University-Purdue University Indianapolis (IUPUI) / Sensitization to the locomotor stimulant effects of alcohol (ethanol) is thought to be a heritable risk factor for the development of alcoholism that reflects progressive increases in the positive motivational effects of this substance. However, very little is known about the genetic influences involved in this phenomenon or the extent to which ethanol’s positive motivational effects are altered in parallel to its development. The first goal of this work was to determine the heritability of ethanol-induced locomotor sensitization in mice using short-term behavioral selection. Genetically heterogeneous C57BL/6J (B6) x DBA/2J (D2) F2 mice were generated from B6D2F1 progenitors, phenotyped for the expression of locomotor sensitization, and bred for high (HLS) and low (LLS) expression of this behavior. A secondary goal was to characterize possible line differences in ethanol’s positive motivational effects using a conditioned place preference assay. There were large and significant differences in locomotor sensitization between HLS and LLS lines by the fourth generation. Twenty-two percent of the observed line difference(s) were attributable to genes (h2=.22). However, there were no significant differences in conditioned place preference between lines despite significant line differences in ethanol-stimulated locomotion following repeated exposures. The results of this work have several implications. First, that changes in ethanol sensitivity following repeated exposures are in part genetically regulated highlights the relevance of studies aimed at determining how genes regulate susceptibility to ethanol-induced behavioral and neural adaptations. Additionally, the lack of line differences in ethanol-induced CPP, and the observation that CPP and ethanol sensitization are dissociable, suggests that 1) different genes regulate these two behaviors and 2) the utility of locomotor sensitization as a model of alterations in ethanol’s positive motivational effects is, at best, still unclear. Together these studies provide evidence that genes are capable of regulating alterations in ethanol-induced locomotor behavior but provide little support for ethanol-induced locomotor sensitization as a model for increases in ethanol’s positive subjective effects in mice.