Modification of Acoustic Startle Reactivity by Cocaine Administration During the Postnatal Period: Comparison With a Specific Serotonin Reuptake Inhibitor

Abstract

This study investigated whether exposure to cocaine during the postnatal period affects the acoustic startle response (ASR) following administration of the serotonin (5-HT) agonists, 8-OH-DPAT and mCPP , in adulthood. To test the hypothesis that alterations in reactivity may be due to cocaine's effects at the 5-HT carrier, another group of rats was given fluoxetine, a specific 5-HT uptake inhibitor, during the same postnatal period and tested along with the cocaine-treated rats. Male and female rats received 25 mg/kg/day cocaine HCl, fluoxetine HCl, or vehicle SC during postnatal days 11–20. At 75 days of age, subjects were ASR tested for 30 min on 2 consecutive days. On the first test day, there was a significant effect of treatment and gender with post hoc analysis indicating that, overall, the males were more reactive than the females and that the fluoxetine-treated males showed a pattern of reactivity resembling sensitization. On the second test day, subjects received a dose of the 5-HT 1A agonist 8-OH-DPAT, the 5- HT 1 B 2 C agonist, mCPP , or saline prior to being placed in the startle chamber. Cocaine-exposed males showed an enhanced response to 8-OH-DPAT and a reduction in the depression produced by mCPP administration compared to their response to saline. Fluoxetine exposed males showed a significant increase in startle response following saline administration compared to the rats receiving vehicle during the postnatal period and 8-OH-DPAT produced an insignificant enhancement of that startle response. mCPP reduced startle in fluoxetine-treated males as it did in the postnatal vehicle-treated controls. In females, the postnatal cocaine and fluoxetine treatments did not alter the response to 8-OH-DPAT or mCPP compared to females receiving vehicle during the postnatal period. Together these data indicate that, in males, whereas postnatal cocaine alters the development of the 5-HT system as evidenced by an altered startle response to 5-HT agonists, cocaine does not produce the same alteration as that produced by the administration of a specific 5-HT uptake inhibitor during the same period of development.