Abstract
Endogenous opioid systems are implicated in the actions of ethanol. For example, μ-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 GABAA 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.
Footnotes
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This study was supported by the National Institute on Alcohol Abuse and Alcoholism Integrative Neuroscience Initiative on Alcoholism [Grant UO1 AA013498]; by the National Institute on Drug Abuse [Grant R01 DA03665]; and by VA Merit Review [Grant 01160/0012].
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.140749.
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ABBREVIATIONS: WT, wild type; MOR, μ-opioid receptor; KO, knockout; CeA, central nucleus of the amygdala; NMDA, N-methyl-d-aspartate; ACSF, artificial cerebrospinal fluid; IPSP, inhibitory postsynaptic potential; IPSC, inhibitory postsynaptic current; EPSC, excitatory postsynaptic current; AP-5, d-2-amino-5-phosphonovalerate; CGP 55845, 3-N[1-(S)-(3,4-dichlorophenyl)ethyl]amino-2-(S)-hydroxypropyl-p-benzyl-phosphinic acid; TTX, tetrodotoxin; sIPSC, spontaneous IPSC; sEPSC, spontaneous EPSC; mIPSC, miniature IPSC; mEPSC, miniature EPSC; DAMGO, [d-Ala2,N-Me-Phe4,Gly5-ol]-enkephalin; naloxonazine, bis-[5-a-4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-morph inan-6-ylidene] hydrazine dihydrochloride; PPR, paired-pulse ratio; ANOVA, analysis of variance; RMP, resting membrane potential; VTA, ventral tegmental area; DOR, δ-opioid receptor; QX 314, N-(2,6-dimethylphenylcarbamoylmethyl)triethylammonium bromide.
- Received May 12, 2008.
- Accepted October 10, 2008.
- U.S. Government work not protected by U.S. copyright
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