Presynaptic delta opioid receptors regulate ethanol actions in central amygdala.
Endogenous opioid systems are implicated in the reinforcing effects of ethanol consumption. For example, delta opioid receptor (DOR) knockout (KO) mice show greater ethanol consumption than wild-type (WT) mice (Roberts et al., 2001). To explore the neurobiological correlates underlying these behaviors, we examined effects of acute ethanol application in brain slices from DOR KO mice using whole-cell patch recording techniques. We examined the central nucleus of amygdala (CeA) because the CeA is implicated in alcohol reinforcement (Koob et al., 1998). We found that the acute ethanol effects on GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) were greater in DOR KO mice than in WT mice. Ethanol increased the frequency of miniature IPSCs (mIPSCs) significantly more in DOR KO mice than in WT mice. In CeA of WT mice, application of ICI 174864 [[allyl]2-Tyr-alpha-amino-isobutyric acid (Aib)-Aib-Phe-Leu-OH], a DOR inverse agonist, augmented ethanol actions on mIPSC frequency comparable with ethanol effects seen in DOR KO mice. Superfusion of the selective DOR agonist D-Pen(2),D-Pen(5)-enkephalin decreased the mean frequency of mIPSCs; this effect was reversed by the DOR antagonist naltrindole. These findings suggest that endogenous opioids may reduce ethanol actions on IPSCs of CeA neurons in WT mice through DOR-mediated inhibition of GABA release and that the increased ethanol effect on IPSCs in CeA of DOR KO mice could be, at least in part, due to absence of DOR-mediated inhibition of GABA release. This result supports the hypothesis that endogenous opioid peptides modulate the ethanol-induced augmentation of GABA(A) receptor-dependent circuitry in CeA (Roberto et al., 2003).
Kang-Park
Maeng-Hee
MH
Department of Psychiatry, Duke University Medical Center, Durham, NC, USA.
Kieffer
Brigitte L
BL
Roberts
Amanda J
AJ
Siggins
George Robert
GR
Moore
Scott D
SD
D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D020881:Enkephalin, D-Penicillamine (2,5)- / Q000494:pharmacology; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011963:Receptors, GABA-A / Q000502:physiology; D017465:Receptors, Opioid, delta / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D011963:Receptors, GABA-A; D017465:Receptors, Opioid, delta; D000431:Ethanol; D005680:gamma-Aminobutyric Acid; D004743:Enkephalin, Leucine; D020881:Enkephalin, D-Penicillamine (2,5)-; C040643:N,N-diallyl-tyrosyl-alpha-aminoisobutyric acid-phenylalanyl-leucine