Amphetamine exerts anomalous effects on dopaminergic neurons in neonatal rats in vivo

The effects of amphetamine, apomorphine and haloperidol on the spontaneous activity of electrophysiologically identified nigral dopaminergic neurons were examined with extracellular recordings in vivo in neonatal rats ranging in age from postnatal day 1 to postnatal day 28, and in adult rats. In postnatal day 1-6 pups amphetamine (5 mg/kg i.p.) produced a paradoxical increase in neuronal firing in 45% and had no effect on 30% of the 20 neurons examined. During the second week half of the neurons recorded were unresponsive to amphetamine. Typical amphetamine-induced inhibition was observed in only 25% of the neurons from postnatal day 1-6 and 50% of those from postnatal day 7-15 rats compared to 81.8% in postnatal day 16-28 pups and 100% in adults. Apomorphine (50-200 micrograms/kg i.p.; 5-20 micrograms/kg i.v.), significantly inhibited the spontaneous activity of dopaminergic neurons, including cells that previously failed to be inhibited by amphetamine, independent of age. The apomorphine-induced inhibition was consistently reversed by administration of haloperidol (0.5-2.0 mg/kg, i.p.; 50-200 micrograms/kg i.v.). The anomalous responses to amphetamine in early neonatal rats may be related to its paradoxical behavioral effects in human children afflicted with attention deficit disorder.