Effects of inhalation exposures and intraperitoneal injections of methyl n-amyl ketone on multiple fixed-ratio, fixed-interval response rates in rats

Twelve rats were tested daily for 1 hr on a multiple fixed-ratio, fixed-interval schedule of reinforcement. The rats were given ip injections of methyl n-amyl ketone (MAK; 2-heptanone), an industrial solvent, in concentrations ranging from 18 to 175 mg/kg on one to eight occasions each, and were tested 15 min after the injections. When compared to the preceding control (saline) day, there was little or no fixed interval (FI) response rate change at 18 mg/kg, moderate FI rate decreases at 37 and 74 mg/kg and a near cessation of responding at 175 mg/kg MAK. Changes were statistically significant (p<0.01) at 37, 74, and 175 mg/kg. The quantity of MAK which altered behavior was about 5% of the dose that was subsequently determined to be lethal to two-thirds of the test animals. Time course data indicated that the behavioral changes seen at 15 min after 175 mg/kg injections persisted for at least 1 hr but had vanished by 2.25 hr after the injections. Over the course of the study, there was a consistent reduction in the magnitude of the behavioral changes, suggesting that tolerance developed. Inhalation exposures below 1500 ppm did not cause behavioral changes, but those in excess of 1575 ppm had effects similar to the 175 mg/kg injections when testing began 5-10 min after termination of the inhalation exposure. However, a lack of opportunity for replications made it impossible to achieve statistical significance.