Low dose cocaine self-administration transiently increases but high dose cocaine persistently decreases brain reward function in rats.

This study investigated the effects of self-administered cocaine on brain reward function, measured by intracranial self-stimulation (ICSS) reward thresholds in rats. Self-administration of 10 and 20 cocaine injections (0.25 mg per injection, equivalent to 4.94 +/- 0.23 and 9.88 +/- 0.46 mg/kg, self-administered over 40 +/- 6.9 and 99 +/- 11.9 min, respectively) lowered reward thresholds 15 min later, indicating a facilitation of rewarding ICSS, but had no effect at 2, 24 or 48 h after administration. Thus, self-administration of low cocaine doses did not cause persistent changes in brain reward function. Forty cocaine injections (19.64 +/- 0.94 mg/kg; self-administered over 185 +/- 10.9 min) also transiently lowered reward thresholds 15 min later, while significant threshold current elevations were observed at 2 and 24 h after administration, indicating persistent withdrawal-like reward deficits. Finally, 80 cocaine injections (39.53 +/- 1.84 mg/kg, self-administered over 376 +/- 19.9 min) significantly elevated thresholds 2 and 48 h after self-administration, but not at 24 h. Threshold currents also tended to be elevated 15 min after self-administration. Overall, these data suggest that as the amount of self-administered cocaine increases the motivation to consume further cocaine may be shifted, from obtaining the rewarding actions of cocaine to avoidance and alleviation of a cocaine-induced negative affective state.