Behavioral effects of chronic cocaine treatment in the week-old rat pup.

Chronic treatment of adult animals with cocaine results in sensitization to some behavioral effects and tolerance to others but there are few reports on the effects of chronic stimulants during early development. The present experiments assessed the development of cocaine-induced alterations in locomotor activity and separation induced ultrasonic vocalization, a fundamental behavior of infant rats. The first study demonstrated a dose dependent suppression of ultrasounds in naive pups at 7 days of age that lasted at least 60 min and that was accompanied by a dose dependent increase in locomotion. To assess chronic effects, pups were injected with cocaine (5.0-30.0 mg/kg) twice daily from ages 1 to 7 days and then tested at 7, 8 and 10 days of age for vocalization in response to isolation from the dam and littermates. There were minimal effects on baseline levels of crying, but following chronic treatment with cocaine, pups showed generally higher levels of ultrasounds when tested with an acute challenge of cocaine at 7 and 8 days of age. In chronically treated pups locomotor activity was increased during baseline tests. At 10 days of age, 3 days after the last treatment with cocaine, in the highest dose treatment condition, there was an exaggerated reduction of ultrasounds when tested with a littermate. The results demonstrate that chronic exposure to cocaine during early development disrupts the normal regulation of a developmentally important socially mediated behavior.