Ethanol self-administration in mice under a second-order schedule.

Long Fixed-Interval (FI) schedules, particularly second-order schedules, can engender substantial responding before drug or ethanol delivery that is uninfluenced by the direct effects of the drug or ethanol. Thus, these schedules can be used to study the effects of medications upon drug- or ethanol-seeking, uninfluenced by the direct effects of the self-administered drug or ethanol. Long FI second-order schedules are frequently used in primates and occasionally in rats. Under second-order schedules, completion of one response requirement, e.g., a Fixed Ratio 10 (FR10:S), produces a brief stimulus presentation, e.g., a 1-s 80-dB 4-kHZ tone, and this FR10:S serves as the response unit under another schedule, e.g., an FI 1800-s. Thus, the first FR10 completed after 1800 s would result in delivery both of the tone and of reinforcement, e.g., 10 × 0.01 mL 16% (w/v) ethanol. To examine if such schedules could be effectively used in mice, which have advantages in neurobiological and genetic studies, we trained eight C57BL/6J mice to respond under the schedule just described. This schedule maintained substantial responding. The temporal pattern of behavior was typical of an FI schedule with responding accelerating across the interval. We also examined the effects of acute and chronic administration of fluvoxamine on this responding, and these were modest. Finally, we examined responding when alcohol and/or tone deliveries were withheld, and found that extinction occurred most rapidly when both were withheld. This work demonstrates that long FI schedules of ethanol delivery may be useful in studying ethanol seeking in mice.