Amphetamine and stress responses in developmentally lead-exposed rats

In this study, pregnant Wistar dams were exposed to 220 ppm of lead (Pb) in drinking water during gestation and lactation. The response to the locomotor-stimulating effects of 0.5 mg/kg of amphetamine (AMPH) was evaluated in 35-day-old male offspring. The results demonstrated that developmental Pb exposure induced no differences in the response to the drug, although an increase in locomotor activity induced by a single saline (SAL) injection was observed selectively in the Pb-exposed group. Considering evidence that suggests a relationship between increased locomotor activity and stress response, a time course analysis of corticosterone (CS) secretion and locomotor performance was carried out. Higher basal levels of CS and elevated stress-induced secretion of this hormone in response to the injection were observed in Pb-exposed rats compared to controls, a pattern that showed a time-related increase in locomotor activity. Habituation to SAL injections prior to testing restored both CS secretion and locomotor response to SAL to levels comparable to controls and did not modify AMPH locomotor response measured in these new experimental conditions. Additionally, we demonstrated that these behavioral/hormonal disruptions were no longer detectable later in adulthood. Collectively, these data suggest that the stimulant-locomotor effect of AMPH in Pb-exposed rats is independent of the arousal of the animal at the time of its administration. They also support a unique profile of integrated behavioral and hormonal hyperresponsiveness in 35-day-old low-level Pb-exposed rats evidenced as hyperlocomotion and altered secretion of CS in response to an environmental manipulation, an effect that was no longer present later in life.