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

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Abstract
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.

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