GABAergic actions mediate opposite ethanol effects on dopaminergic neurons in the anterior and posterior ventral tegmental area.
It is known that the posterior ventral tegmental area (p-VTA) differs from the anterior VTA (a-VTA) in that rats learn to self-administer ethanol into the p-VTA, but not into the a-VTA. Because activation of VTA dopaminergic neurons by ethanol is a cellular mechanism underlying the reinforcement of ethanol consumption, we hypothesized that ethanol may exert different effects on dopaminergic neurons in the p-VTA and a-VTA. In patch-clamp recordings in midbrain slices from young rats (postnatal days 22-32), we detected no significant difference in electrophysiological properties between p-VTA and a-VTA dopaminergic neurons. However, acute exposure to ethanol (21-86 mM) stimulated p-VTA dopaminergic neurons but suppressed a-VTA dopaminergic neurons. Conversely, ethanol (>21 mM) dose-dependently reduced the frequency of the GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs) generated by inhibitory neuronal firing but not miniature inhibitory postsynaptic currents (mIPSCs) in p-VTA dopaminergic neurons. By contrast, ethanol increased the frequency and amplitude of both sIPSCs and mIPSCs in a-VTA dopaminergic neurons. All of these effects of ethanol were abolished by a GABA(A) receptor antagonist. There was a strong negative correlation between ethanol-evoked modulation of sIPSCs and neuronal firing in VTA dopaminergic neurons. These results indicate that GABAergic inputs play an important role in ethanol's actions in the VTA. The differential effects of ethanol on sIPSCs and neuronal firing in the p-VTA and a-VTA could be the basis for ethanol reinforcement via the p-VTA.
Department of Anesthesiology, Pharmacology, and Physiology, UMDNJ, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103, USA.
Yanzhong
Y
Guan
Cheng
C
Xiao
Kresimir
K
Krnjevic
Guiqin
G
Xie
Wanhong
W
Zuo
Jiang-Hong
JH
Ye
D000818:Animals; D000831:Animals, Newborn; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000502:physiology*; D000431:Ethanol / Q000494:pharmacology*; D018682:GABA Agents / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D018682:GABA Agents; D000431:Ethanol; D005680:gamma-Aminobutyric Acid