Gamma-aminobutyric acid mediation of the inhibitory effect of endogenous opioids on the arginine vasopressin and oxytocin responses to nicotine from cigarette smoking.
Previous studies have demonstrated that naloxone exerts positive effects on the responsiveness of arginine vasopressin (AVP) and oxytocin (OT) to nicotine, suggesting inhibitory actions of endogenous opioids. The present study was designed to determine whether a gamma-aminobutyric acid (GABA)ergic pathway is involved in the regulation of naloxone-sensitive endogenous opioid action. AVP and OT secretory patterns after (two nonfilter) cigarette smoking were examined in seven normal male subjects with (experimental test) and without (control test) concomitant treatment with naloxone (4 mg in an intravenous bolus plus 6 mg infused over 2 hours), the GABAergic agent sodium valproate (600 mg in three divided doses orally), or the combination of naloxone and sodium valproate. Cigarette smoking increased by 2.4-fold (peak v baseline) the plasma concentrations of AVP without modifying OT levels. In the presence of naloxone, plasma AVP and OT levels in response to nicotine were significantly higher than those in the control test. In the naloxone plus nicotine test, AVP levels increased 4.2-fold (peak v baseline) and OT concentrations increased 1.6-fold (peak v baseline). Pretreatment with sodium valproate changed neither AVP nor OT secretory patterns during the cigarette-smoking test. In contrast, sodium valproate abolished the facilitating effect of naloxone on both AVP and OT responses to nicotine. In the sodium valproate plus naloxone plus nicotine test, plasma AVP and OT levels were not significantly higher than those obtained during the nicotine test. These data indicate a GABAergic mediation of the inhibitory modulation by endogenous opioids of the AVP and OT responses to nicotine.
Cattedra di Endocrinologia e Patologia Costituzionale, Università di Parma, Italy.
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D000328:Adult; D000704:Analysis of Variance; D001127:Arginine Vasopressin / Q000097:blood*; D004347:Drug Interactions; D004723:Endorphins / Q000502:physiology*; D006801:Humans; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology*; D010121:Oxytocin / Q000097:blood*; D012907:Smoking / Q000097:blood*; D014635:Valproic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D004723:Endorphins; D001127:Arginine Vasopressin; D009270:Naloxone; D010121:Oxytocin; D005680:gamma-Aminobutyric Acid; D014635:Valproic Acid; D009538:Nicotine