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Published on: August 4, 2022
Mu-opioid receptors selectively regulate basal inhibitory transmission in the central amygdala: lack of ethanol
Maeng-Hee Kang-Park1, Brigitte L Kieffer, Amanda J Roberts
1Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA.
Abstract:
Endogenous opioid systems are implicated in the actions of ethanol. For example, mu-opioid receptor (MOR) knockout (KO) mice self-administer less alcohol than the genetically intact counterpart wild-type (WT) mice (Roberts et al., 2000). MOR KO mice also exhibit less anxiety-like behavior than WT mice (Filliol et al., 2000). To investigate the neurobiological mechanisms underlying these behaviors, we examined the effect of ethanol in brain slices from MOR KO and WT mice using sharp-electrode and whole-cell patch recording techniques. We focused our study in the central nucleus of the amygdala (CeA) because it is implicated in alcohol drinking behavior and stress behavior. We found that the amplitudes of evoked inhibitory postsynaptic currents (IPSCs) or inhibitory postsynaptic potentials (IPSPs) were significantly greater in MOR KO mice than WT mice. In addition, the baseline frequencies of spontaneous and miniature GABA(A) receptor-mediated inhibitory postsynaptic currents were significantly greater in CeA neurons from MOR KO than WT mice. However, ethanol enhancements of evoked IPSP and IPSC amplitudes and the frequency of miniature IPSCs were comparable between WT and MOR KO mice. Baseline spontaneous and miniature excitatory postsynaptic currents (EPSCs) and ethanol effects on EPSCs were not significantly different between MOR KO and WT mice. Based on knowledge of CeA circuitry and projections, we hypothesize that the role of MOR- and GABA receptor-mediated mechanisms in CeA underlying reinforcing effects of ethanol operate independently, possibly through pathway-specific responses within CeA.
Insights
Mu-opioid receptor (MOR) knockout mice show altered inhibitory signaling in the central amygdala (CeA). Ethanol
Area of Science:
- Neuroscience
- Pharmacology
- Genetics
Background:
- Endogenous opioid systems, particularly mu-opioid receptors (MOR), influence ethanol's effects.
- MOR knockout mice exhibit reduced alcohol self-administration and anxiety-like behaviors compared to wild-type mice.
- The central nucleus of the amygdala (CeA) is crucial for regulating alcohol and stress-related behaviors.
Purpose of the Study:
- To investigate the neurobiological mechanisms of ethanol's action in the CeA.
- To compare the effects of ethanol on neuronal activity in MOR knockout and wild-type mice.
- To elucidate the roles of MOR and GABAergic systems in ethanol's reinforcing effects.
Main Methods:
- Electrophysiological recordings (sharp-electrode and whole-cell patch) were performed on brain slices.
- Examines evoked and spontaneous inhibitory postsynaptic currents (IPSCs) and potentials (IPSPs).
- Analyzes spontaneous and miniature excitatory postsynaptic currents (EPSCs) in CeA neurons.
Main Results:
- MOR knockout mice displayed significantly greater evoked IPSC/IPSP amplitudes and GABA(A) receptor-mediated inhibitory postsynaptic current frequencies in CeA neurons.
- Ethanol's enhancement of evoked IPSPs/IPSCs and miniature IPSC frequency was similar in both MOR knockout and wild-type mice.
- No significant differences in baseline or ethanol-affected excitatory postsynaptic currents (EPSCs) were observed between genotypes.
Conclusions:
- MOR knockout alters baseline inhibitory neurotransmission in the CeA.
- MOR- and GABA receptor-mediated mechanisms in the CeA may independently contribute to ethanol's reinforcing effects.
- Pathway-specific neuronal responses within the CeA could underlie these independent mechanisms.
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