Archival ReportLess Is More: Antipsychotic Drug Effects Are Greater with Transient Rather Than Continuous Delivery
Section snippets
Methods and Materials
Male Sprague Dawley rats (Charles River Laboratories, Montreal, PQ, Canada) weighing 225 g to 250 g were housed two per cage in a climate-controlled colony room with a 12-hour reverse light/dark cycle (lights off at 8:00 am). Food and water were available ad libitum. All testing was conducted during the dark phase of the animals' circadian cycle and was in compliance with the institute's animal care committee.
Experiment 1: Effects of the kinetics of HAL Treatment on Behavioral Sensitivity to AMPH Over Time
In Experiment 1, we examined the effects of the kinetics of chronic antipsychotic drug administration (achieved by administering HAL via minipump or daily SC injection) on the suppression of AMPH-induced locomotion over time. The locomotor response to AMPH in the HAL-.05 CONT rats was not different from control animals at any time point tested. Early in treatment (day 2; Figure 2A), AMPH-induced locomotion was suppressed in both the HAL-.5 CONT and HAL-TRANS groups to a similar degree. With
Discussion
We show here that chronic treatment with an antipsychotic, using the same achieved dose and route of administration but different treatment kinetics (i.e., within-day continuous versus transient), leads to tolerance to ongoing antipsychotic treatment in one case and progressively increasing efficacy in the other. Transient treatment was more effective than continuous treatment even when a 10-fold lower dose was administered using the transient mode, thus producing greater efficacy with lesser
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