Modification of acoustic startle reactivity by cocaine administration during the postnatal period: comparison with a specific serotonin reuptake inhibitor.
This study investigated whether exposure to cocaine during 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-HT1A agonist 8-OH-DPAT, the 5-HT1B/2C 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.
Dow-Edwards
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Department of Pharmacology, State University of New York Health Science Center, Brooklyn 11203, USA.
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D003042:Cocaine / Q000494:pharmacology*; D005260:Female; D005473:Fluoxetine / Q000494:pharmacology*; D008297:Male; D009294:Narcotics / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D003042:Cocaine; D005473:Fluoxetine; D009294:Narcotics; D010879:Piperazines; D017366:Serotonin Receptor Agonists; D017367:Selective Serotonin Reuptake Inhibitors; C015068:1-(3-chlorophenyl)piperazine