Vol. 297, Issue 2, 746-752, May 2001

Amphetamine Normalizes the Electrical Activity of Dopamine Neurons in the Ventral Tegmental Area following Prenatal Ethanol Exposure

Changqing Xu and Roh-Yu Shen

Research Institute on Addictions, University at Buffalo, State University of New York, Buffalo, New York

Prenatal ethanol exposure has been shown to produce a persistent reduction in the spontaneous activity of ventral tegmental area (VTA) dopamine (DA) neurons and in DA neurotransmission. Amphetamine-like stimulants are effective in treating attention deficit/hyperactivity disorder (ADHD), which is a major symptom in fetal alcohol syndrome. Because there is a link between reduced DA neurotransmission and ADHD, we investigated the possibility that amphetamine could restore the spontaneous activity of VTA DA neurons. Pregnant rats were administered 0 or 6 g/kg/day ethanol via intragastric intubation during gestation days 8 to 20. The spontaneous activity of VTA neurons was studied in 6- to 8-week-old male offspring using extracellular single-unit recording in unanesthetized (paralyzed, locally anesthetized) or chloral hydrate-anesthetized rats. Prenatal ethanol exposure reduced the number of spontaneously active DA neurons without changing the firing rate or firing pattern in both groups of animals. Acute amphetamine administration (2 mg/kg, i.v.) increased the number of spontaneously active DA neurons after prenatal ethanol exposure. Because amphetamine inhibited DA neuron firing rate in ethanol-exposed animals, it is possible that amphetamine restored the number of spontaneously active neurons by alleviating the depolarization block. These results show that the reduction in the number of spontaneously active DA neurons resulting from prenatal ethanol exposure is not confounded by using general anesthesia. Furthermore, acute amphetamine treatment can normalize the activity of DA neurons after prenatal ethanol exposure. This mechanism may contribute to the therapeutic effects of amphetamine-like stimulants in attention problems observed in children with fetal alcohol syndrome.