Differential interaction between stressors and chronic amphetamine or phencyclidine upon operant behavior in the rat

Three types of stress were examined for their effects upon fixed-ratio 15 (FR-15) operant behavior in Sprague-Dawley rats before and after chronic dextroamphetamine to determine if cumulated drug could interact with stress to produce a state of behavioral toxicity. Six daily s.c. injections of saline were given to rats following 30 min behavioral sessions. Thirty minutes of exposure to a cold environment (7 degrees C) or to electric footshock (2mA for 0.5 sec, 1 shock/min) had no significant effect upon FR-15 behaviour beginning 15 min afterward. Five daily s.c. injections of 2.5 mg dextroamphetamine/kg after behavioral sessions suppressed behavior during the following days an average of 12%. Rats were again stressed twenty-two hours after the sixth injection. Footshock further suppressed behavior to 26% of the unstressed, chronic amphetamine-treated control group. Cold exposure failed to suppress behavior significantly below control levels. A similar experiment employing cold water exposure (15 degrees C for 2 min) as the stressor showed that, although, this stressor suppressed FR-15 behavior to 53% of the previous day's rates and reduced body temperature 2.1 degree C, chronic amphetamine failed to interact with the cold water stress to suppress behavior further. In a third experiment, 4.5 mg phencyclidine/kg, s.c., given after 30-min FR-15 sessions for six days, failed to interact with the footshock stress to cause behavioral suppression different from control treatment. While stress can interact with chronic treatment with lipophilic drugs, the quality of the stress, and the physical and pharmacologic properties of the drug are important determinants of the outcome upon conditioned behavior.