Dose-dependent transitions in nucleus accumbens cell firing and behavioral responding during cocaine self-administration sessions in rats.

At the initiation of cocaine self-administration sessions, neurons in the rat nucleus accumbens (NA) exhibit a spontaneous transition in firing rate from activity unrelated to the reinforced response to one of four types of patterned discharges. This transition in NA activity is accompanied by a shift from high response rates at the start of the session ("Load-Up" behavior) to a lower rate for the remainder of the session. In this study, the relationship between transitions in behavioral responding and NA activity was examined further by changing the dose of cocaine per session (0.66, 0.50, 0.33, 0.16 or 0.08 mg/inf). Results show that the number of Load-Up responses significantly increased at lower cocaine doses [0.16, 0.08 mg/infusion (inf)] and decreased at higher doses (0.33, 0.50, 0.66 mg/inf). Thereafter, animals responded either with regularly spaced interinfusion intervals (INTs) at high doses (0.33, 0.50 and 0.66 mg/inf), or frequent bursts and pauses in responding at low doses (0.16 and 0.08 mg/inf. NA neurons exhibited a spontaneous transition in firing rate that was significantly correlated with this shift in behavioral responding across different doses of cocaine. Pretreatment with the dopamine D1 receptor antagonist SCH23390 (5 or 10 microgram/kg) prolonged the onset of NA patterned discharges, similar to responding for low doses of cocaine (0.08 and 0.16 mg/inf. These findings are discussed in terms of a functional role of the NA in mediating the reinforcing properties of cocaine.