Reserpine differentially affects cocaine-induced behavior in low and high responders to novelty.

Individuals are known to differ in their sensitivity to cocaine. Cocaine is known to inhibit the re-uptake of monoamines. The response to cocaine has also been found to depend on monoamines inside reserpine-sensitive storage vesicles. The present study examined the effects of reserpine (1-2 mg/kg) on cocaine-induced behavior (10-15 mg/kg) in Low Responders (LR) and High Responders (HR) to novelty rats. LR displayed less cocaine-induced walking, wall rearing, free rearing and stereotyped behavior than HR did. The dose of 1 mg/kg of reserpine decreased cocaine-induced walking, wall rearing, free rearing and stereotyped behavior in LR, but not in HR. A dose of 2 mg/kg of reserpine was required to inhibit cocaine-induced behavior in HR. Combining these behavioral findings with our previously reported neurochemical finding that a higher dose of reserpine was required to inhibit the accumbal dopamine response to cocaine in HR than in LR (Verheij et al., 2008), suggests that HR are more sensitive to the behavioral effects of cocaine than LR because cocaine can release more monoamines from storage vesicles in HR than in LR. Our behavioral data also demonstrate that the individual differences in sensitivity to reserpine are not only limited to the dopaminergic system of the nucleus accumbens.