Description:
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In this research we examined the mechanisms by which ethanol (EtOH) inhibits luteinizing hormone-releasing hormone (LHRH) release from incubated medial basal hypothalamic explants. EtOH (100 mM) stimulated the release of two inhibitory neurotransmitters: γ-aminobutyric acid (GABA) and β-endorphin. EtOH also inhibited NO production, indicative of a suppression of nitric oxide synthase (NOS) activity. This inhibition was reversed by naltroxone (10
<jats:sup>−8</jats:sup>
M), a μ-opioid receptor blocker, indicating that the inhibition of NOS by EtOH is mediated by β-endorphin. EtOH also blocked
<jats:italic>N-</jats:italic>
methyl-
<jats:sc>d</jats:sc>
-aspartic acid-induced LHRH release, but the blockade could not be reversed by either the GABA receptor blocker, bicuculline (10
<jats:sup>−5</jats:sup>
M), naltroxone (10
<jats:sup>−8</jats:sup>
M), or both inhibitors added together. However, increasing the concentration of naltrexone (10
<jats:sup>−6</jats:sup>
M) but not bicuculline (10
<jats:sup>−4</jats:sup>
M) reversed the inhibition. When we lowered the concentration of EtOH (50 mM), the EtOH-induced blockade of LHRH release could be reversed by either bicuculline (10
<jats:sup>−5</jats:sup>
M), naltroxone (10
<jats:sup>−8</jats:sup>
M), or the combination of the two blockers. Therefore, GABA is partially responsible for the blockade of
<jats:italic>N-</jats:italic>
methyl-
<jats:sc>d</jats:sc>
-aspartic acid-induced LHRH release. The block by GABA was exerted by inhibiting the activation of cyclooxygenase by NO, because it was reversed by prostaglandin E
<jats:sub>2</jats:sub>
, the product of activation of cyclooxygenase. Because the inhibition caused by the higher concentration of EtOH could not be reduced by bicuculline (10
<jats:sup>−4</jats:sup>
M) but was blocked by naltroxone (10
<jats:sup>−6</jats:sup>
M), the action of alcohol can be accounted for by stimulation of β-endorphin neurons that inhibit LHRH release by inhibition of activation of NOS and stimulation of GABA release.
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