Intravenous cocaine self-administration in the C57BL/6J mouse

Freely behaving C57BL/6J mice with intrajugular catheters were trained to nose-poke for cocaine (0.75 mg/kg per 5-μ1 infusion) under a fixed-ratio-10 schedule of reinforcement. Mice were given a choice between two nose-poke holes on opposite sides of the apparatus. Nose-pokes by experimental (O) subjects (operant group) were reinforced on only one side and reinforcer delivery coincided with the onset of a 10-s time-out light stimulus. Drug delivery to control subjects (yoked group) was determined by the behavior of O mice. Nose-poke rate increased in O subjects, whereas yoked subjects did not acquire the nose-poking response. Moreover, nose-poking was selective for the cocaine-paired side in O subjects. When saline infusions were substituted for cocaine (i.e., extinction), nose-poking in O subjects decreased, whereas yoked controls were unaffected. O subjects developed a preference for the drug-associated side of the apparatus during extinction. Overall, these data offer strong evidence of cocaine-directed behavior in the C57BL/6 inbred mouse strain. More generally, these findings support the feasibility of using intravenous self-administration to assess reinforcement in genetically well-defined populations.