Mu-opioid receptors selectively regulate basal inhibitory transmission in the central amygdala: lack of ethanol interactions.
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.
Department of Psychiatry, Duke University Medical Center, Durham, North Carolina, USA.
Maeng-Hee
MH
Kang-Park
Brigitte L
BL
Kieffer
Amanda J
AJ
Roberts
Marisa
M
Roberto
Samuel G
SG
Madamba
George Robert
GR
Siggins
Scott D
SD
Moore
D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D003433:Crosses, Genetic; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018408:Patch-Clamp Techniques; D017450:Receptors, Opioid, mu / Q000172:deficiency / Q000187:drug effects / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D017450:Receptors, Opioid, mu; D000431:Ethanol