Our objective is to advance the behavioral pharmacology and toxicology of inhalants. The development of models of inhalant abuse will provide techniques that: (1) permit assessment of the relative abuse potential of solvents and anesthetics; (2) permit specification of nontoxic levels of solvent exposure and the establishment of industrial exposure limit values; (3) permit comparison of the strength of inhalant-maintained drug-seeking behavior with the strength of behavior maintained by other drugs of abuse. The proposed program will progress in parallel phases: 1) Solvent self-administration by the monkey. Monkeys will be trained to self-administer inhalants such as alkyl benzenes (e.g. toluene), ketones, and aliphatic alcohols. Concentration- and duration-effect curves will be determined. Schedules of reinforcement will be examined to determine the effectiveness of these agents as reinforcers. Blood levels of the inhalants will be determined. 2) Aversive properties of inhaled substances. We will generate performances maintained by the termination of exposure to noxious volatile substances. The initial aversiveness of solvents may play an important role in determining their abuse potential. The ways that volatile materials can be made aversive are of paramount importance, and could bear directly on the regulation of consumer products. 3) Effects of organic solvents on performance. Inhaled materials also induce behavioral toxicity that can be measured by using schedule-controlled behavior. Concentration-effect curves of several agents will be obtained to determine how concentrations that maintain self-administration are related to those that affect other performances. Knowledge of such effects helps us characterize the pharmacologic profile of these agents and, in conjunction with self-administration and pharmacokinetic data, helps us undertstand the determinants of inhalant abuse.
