NeuropharmacologyEthanol dually modulates GABAergic synaptic transmission onto dopaminergic neurons in ventral tegmental area: Role of μ-opioid receptors
Section snippets
Experimental procedures
All experiments were performed in accordance with the guidelines of the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were approved by the Institutional Animal Care and Use Committee of the University of Medicine and Dentistry of New Jersey. All efforts were made to minimize animal suffering and to reduce the number of animal used. The experiments were performed on Sprague–Dawley rats aged 14–28 postnatal (P) days.
Ethanol depresses GABAA-receptor-mediated IPSCs of VTA DA neurons
Monosynaptic eIPSCs were evoked in the presence of APV (50 μM) and DNQX (20 μM) at a holding potential of 0 mV; their suppression by BIC (10 μM; Fig. 1A) confirmed that they were mediated by GABAA receptors. As illustrated in Fig. 1A and C, ethanol (40 mM) significantly and reversibly diminished the peak amplitude of eIPSCs (by 23±3%, n=6, P<0.001). To determine whether ethanol inhibits GABAergic synaptic transmission via a pre- or a post-synaptic mechanism, we recorded eIPSCs in response to a
Discussion
Ethanol, at clinically relevant concentrations (10–40 mM) strongly suppressed action potential–dependent GABAergic synaptic transmission onto VTA DA neurons in acute midbrain slices of rats. DAMGO, a MOR agonist mimicked ethanol-induced inhibition of GABAergic transmission. Due to the fact that MORs are mostly expressed on the soma and dendritic area of GABAergic neurons in VTA, this result suggests that ethanol inhibition probably results from suppression of GABAergic neurons in VTA. In
Conclusion
In conclusion, our findings support growing evidence that VTA GABAergic transmission is a crucial target of ethanol.
Acknowledgments
This work was supported by grant AA015925 and AA016964 from the National Institute of Alcohol Abuse and Alcoholism (NIAAA) of the NIH.
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