Post-sensitisation conditioned hyperlocomotion induced by cocaine is augmented as a function of dose in C57BL/6J mice

The study tested the possibility of a positive relationship between the dose of cocaine and the size of the placebo effect generated after contextual sensitisation to the behavioural effects of cocaine. Male C57BL/6J mice were first injected (subcutaneous, s.c.) over seven successive daily sessions with saline or one of three doses of cocaine (2.5, 5 or 7.5 mg/kg), either in the test room or in the colony room (before being placed in a novel cage tub). On the test day, 24 h after chronic pre-treatment, mice from the four conditions were challenged under saline in the test room. Mice were video-recorded and their behaviours were scored using a time-sampling technique. A dose-dependent development of sensitisation was first generated. On the saline challenge test day, significant levels of placebo hyperlocomotion were obtained for mice previously given 5 and 7.5 mg/kg, but not 2.5 mg/kg cocaine, the effect being significantly greater in the mice pretreated with the highest dose than in those receiving the intermediate one, which exhibited a placebo effect that was greater than that of the mice pretreated with 2.5 mg/kg cocaine. Therefore, the magnitude of the placebo effect was a function of the intensity of the unconditioned stimulus (the dose used to generate sensitisation). Such results directly support the Pavlovian conditioning account of post-sensitisation placebo effects.