Intravenous cocaine self-administration in a panel of inbred mouse strains differing in acute locomotor sensitivity to cocaine

We conclude that acute cocaine-induced locomotor activation does predict self-administration behavior, but in a strain-specific manner. These data support the idea that genetic background influences the relationship among addiction-related behaviors.

We selected eight inbred mouse strains based on locomotor sensitivity to 20 mg/kg cocaine. These strains, designated as low and high responders, were tested in an intravenous self-administration paradigm that included acquisition of 0.5 mg/(kg*inf) under a FR1 schedule, extinction, re-acquisition, dose response to 0.125, 0.25, 0.5, 1, and 2 mg/(kg*inf), and progressive ratio.

We observed overall differences in self-administration behavior between high and low responders. Low responders self-administered less cocaine and had lower breakpoints under the PR schedule. However, we also observed strain differences within each group. Self-administration in the low responder, LG/J, more closely resembled the behavior of the high-responding group, and the high responder, P/J, had self-administration behavior that more closely resembled the low-responding group. Conclusions: We conclude that acute cocaine-induced locomotor activation does predict self-administration behavior, but in a strain-specific manner. These data support the idea that genetic background influences the relationship among addiction-related behaviors.