Conditioned drug effects and absence of tolerance to d-amphetamine induced motor activity

Rats administered d- methamphetamine 30 min before sessions during the course of repeated injections showed an enhanced response to d-amphetamine during the test for tolerance development, which underscores the importance of learned or conditioned variables that may result from repeated drug administration in conjunction with behavioral tests.

Abstract

Tolerance development to d-amphetamine induced motor motor activity was studied under various experimental conditions. Following seven daily habituation sessions, female, albino rats were subjected to 7 daily sessions in which NaCl was injected IP 30 min before placement into activity cages (NaCl controls). In the next 9 days, the rats underwent 3 drug sessions, each separated by 2 NaCl controls, in which d-amphetamine (0.5, 10. or 1.7 mg/kg) was likewise injected before placement. A course of repeated drug administration followed for the next 14 days. One group of rats was injected with the drug 30 min before placement into the activity cage, a second group received the drug 30 min after each session as a control for conditioned activity effects, while a third group received NaCl. On the fifteenth day, all rats recieved d-aphetamine 30 min before placement as a test for tolerance development. This session was followed the next day by a test for conditioned motor effects in which NaCl was injected IP 30 min before the session. Dose related increases in motor activity were observed during the drug control sessions. The magnitude of the drug effect did not decrease following any of the conditions during the course of repeated drug administration. Animals repeatedly injected with the drug 30 min after or with NaCl 30 min before each session were affected by d-amphetamine approximately the same as they were before repeated injections. Rats administered d-amphetamine 30 min before sessions during the course of repeated injections showed an enhanced response to d-amphetamine during the test for tolerance. The magnitude of the change was related to the magnitude of the conditioned motor activity response. These experiments emphasize the importance of learned or conditioned variables that may result from repeated drug administration in conjunction with behavioral tests.