Numerous inconsistencies in the reported effects of drugs that can be found in both the human clinical and animal experimental literatures have prompted attempts to identify the basis of this variability. Our data suggest that one source may derive from the tendency of many systems to oscillate in their response to repeated drug or stress exposure. In the first experiment a single administration of ethanol to male rats, either 2 or 30 minutes or 2 weeks before sacrifice suppressed amphetamine-induced dopamine efflux from striatal slices. However, when ethanol was given both 2 weeks and 30 minutes before sacrifice, the two treatments significantly attenuate each other's effects. In Experiment 2, the stress of a novel environment (black box) 30 minutes before sacrifice decreased fractional D-[3H]aspartate efflux from the medial frontal cortex. When a single injection of ethanol 1 week earlier was added to black box exposure, it depressed efflux still futher. However, adding a third treatment (ethanol at 2 weeks and 1 week + black box at 30 minutes) significantly reversed the effects of the two treatments (ethanol + black box). When a four-treatment chain was used (ethanol at 3, 2, and 1 week + black box at 30 minutes), the attenuation of efflux was reinstated. These data complement other findings from this laboratory showing that repeated stress or drug exposure can lead to an oscillatory pattern of change in the effects of future exposures and, in this way, contribute to variability in drug responsiveness.
Caggiula, A. R., Antelman, S. M., Palmer, A. M., Kiss, S., Edwards, D. J., & Kocan, D. (1996). The effects of ethanol on striatal dopamine and frontal cortical D-[3H]aspartate efflux oscillate with repeated treatment. Relevance to individual differences in drug responsiveness. Neuropsychopharmacology, 15(2), 125–132. https://doi.org/10.1016/0893-133X(95)00174-C