Effects of prenatal ethanol exposure on the excitability of ventral tegmental area dopamine neurons in vitro.
Prenatal ethanol exposure leads to a persistent reduction in the number of spontaneously active dopaminergic (DA) neurons (DA neuron population activity) in the ventral tegmental area (VTA) in developing and adult animals. This effect might contribute to the dysfunction of the mesolimbic/cortical DA system and attention problems in children with fetal alcohol spectrum disorders. To characterize the underlying cellular mechanism for prenatal ethanol exposure-induced reduction in VTA DA neuron population activity, we used the whole-cell patch-clamp technique to study the membrane properties of putative VTA DA neurons in brain slices in 2- to 3-week-old control and prenatal ethanol-exposed animals. The results show that prenatal ethanol exposure did not impair the spontaneous pacemaker activity in putative VTA DA neurons but reduced the frequency of evoked action potentials. In addition, prenatal ethanol exposure led to a reduction in hyperpolarization-induced cation current (I(h)) and an up-regulation of somatodendritic DA autoreceptors. The above prenatal ethanol exposure-induced changes could decrease the excitability of VTA DA neurons. However, they do not seem to play a role in reduced VTA DA neuron population activity in vivo, an effect thought to be mediated by excessive excitation leading to depolarization inactivation. Taken together, the above results indicate that prenatal ethanol exposure-induced reduction in VTA DA neuron population activity in vivo is not caused by changes in the intrinsic pacemaker activity or other membrane properties and could instead be caused by altered inputs to VTA DA neurons.
Wang
Jue
J
Research Institute on Addictions, 1021 Main St., Buffalo, NY 14203, USA.
Haj-Dahmane
Samir
S
Shen
Roh-Yu
RY
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D017660:Autoreceptors / Q000187:drug effects; D000431:Ethanol / Q000633:toxicity*; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D011954:Receptors, Dopamine / Q000187:drug effects; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000502:physiology
D017660:Autoreceptors; D011954:Receptors, Dopamine; D000431:Ethanol