Serotonergic modulation of rat pup ultrasonic vocal development: studies with 3,4-methylenedioxymethamphetamine

3,4-Methylenedioxymethamphetamine (MDMA) has previously been shown to destroy serotonin terminals in the rat brain. Despite profound and prolonged loss of serotonin innervation, long-term behavioral effects of MDMA have not previously been reported. In this study, we monitored the short- and long-term effects of MDMA administration on the ultrasonic isolation call of the rat pup. At 30 to 60 min after a single dose of MDMA (0.5-10.0 mg/kg), isolation calls decreased as much as 90%, with a rebound increase in calling noted 10 to 25 h following administration of the highest dose. Repeated administration of 10 mg/kg MDMA (once or twice daily on postnatal days 1-4) resulted in a lasting, dose-dependent decrease in ultrasonic vocalization monitored on days 6, 9, 12 and 15. Concurrent measures of locomotor behavior, geotaxis and weight gain were not altered subsequent to repeated MDMA treatment. Both serotonin content and serotonin terminals (assessed by [3H]paroxetine binding) in cortex were reduced by repeated MDMA treatment, whereas concentrations of catecholamines and their metabolites were unaltered. Repeated prenatal MDMA exposure did not affect postnatal rates of calling or the biochemical markers of serotonin in cortex. Pups lesioned with MDMA postnatally showed not only long-term behavioral and biochemical changes but also altered responsiveness to the serotonin 1B agonist 1-[3-(trifluromethyl)phenyl]piperazine. Taken together, these studies indicate that serotonergic lesions in a sensitive phase of development can have long-term selective effects on the rat pup ultrasonic isolation call, a behavior critical for mother-infant affiliation.