Affiliation:
1. U.S. Air Force, Toxicology Division, Armstrong Laboratory, 2856 G Street, Building 79, Wright-Patterson Air Force Base, Dayton, OH 45433-7400, USA.
Abstract
A design feature of most dose-response studies involving schedule-controlled operant behavior is the repeated administration of different doses of the test substance to the same experimental animal. Repeated dosing raises the question of whether or not an animal's initial exposure to a chemical agent alters its behavioral response to subsequent exposures. To address this question, a dose-response curve for the effect of inhaled 1,1,1-trichloroethane (TRI) on the rate of lever-pressing for milk delivery was generated with repeatedly exposed rats (i.e., a within-subject design) and compared to dose-response data obtained from rats receiving a single inhalation exposure to TRI (i.e., a between-group design). Relative to that generated with singly exposed rats, the dose-response curve generated by repeated exposure was shifted to the left. This suggests that the behavioral effects of rate-decreasing concentrations of TRI are augmented by previous exposures. This residual effect is apparently not due to the accumulation of pharmacologically active substances or to the development of an aversion to responding, since TRI is rapidly eliminated following exposure and solvent-free responding was unaffected 24 h postexposure. Instead, the results of this study support the well-established belief that an animal's response to a drug or chemical agent can be modified by its prior behavioral and exposure history. Thus, comparisons of single and repeated exposures may be necessary for fully accurate interpretations of the behavioral consequences of solvent exposure.