title: Central cardiovascular effects of gamma-hydroxybutyric acid: interactions with noradrenaline, serotonin, dopamine and acetylcholine transmission.
abstract: Gamma-hydroxybutyric acid (GHBA) increased arterial blood pressure and heart rate dose-dependently following intraperitoneal and intracerebroventricular administration to conscious rats. Cardiovascular responses to GHBA were completely prevented after pretreatment with reserpine or phenoxybenzamine and after a prehypothalamic brain transection. Intraperitoneal GHBA increased brain noradrenaline (NA) synthesis and utilization, particularly in the neocortex. Selective central NA depletion in combination with NA synthesis inhibition prevented the cardiovascular effects of GHBA. No overt interactions were observed with agents influencing 5-hydroxytryptamine (5-HT), dopamine (DA), or acetylcholine (Ach) transmission. Pentobarbitone but not diazepam or diphenylhydantoin abolished the hypertensive properties of GHBA. We conclude that the cardiovascular effects of GHBA are of central origin and that they are mediated via the peripheral sympathetic nervous system. They are dependent on an intact central NA transmission while there are few indications for a significant role of central DA-, 5-HT or Ach-mechanisms.
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects*; D006885:Hydroxybutyrates / Q000494:pharmacology*; D008297:Male; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism; D012978:Sodium Oxybate; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: D006885:Hydroxybutyrates; D018377:Neurotransmitter Agents; D012701:Serotonin; D012978:Sodium Oxybate; D000109:Acetylcholine; D004298:Dopamine; D009638:Norepinephrine