Action of harman (1-methyl-beta-carboline) on the brain: body temperature and in vivo efflux of 5-HT from hippocampus of the rat.
Harman (1-methyl-beta-carboline) has been shown previously to act on the hippocampus of the rat in terms of its evocation of anxiogenic responses and induction of alcohol preference. In the present experiments, the localized perfusion of 200 microM harman in the dorsal hippocampus of freely moving rats increased the levels of serotonin (5-HT) but not 5-hydroxyindoleacetic acid (5-HIAA) in cerebral dialysates. The systemic administration of 5.0-20 mg/kg harman also enhanced 5-HT in the perfusates but reduced the levels of 5-HIAA in a dose-dependent manner, probably as a result of the inhibition of the enzyme monoamine oxidase type A (MAO-A). Harman given systemically in doses of 2.5-20 mg/kg induced an intense hypothermia, with a maximum fall produced by the 5.0 mg/kg dose. This fall in body temperature (Tb) induced by 5.0 mg/kg harman was not antagonized by 5.0 mg/kg of (+/-)-pindolol. Further, pretreatment of the rats with parachlorophenylalanine (pCPA) also failed to alter the harman-induced hypothermia. The systemic administration of 10 mg/kg of the MAO-A inhibitor, clorgyline, also lowered Tb significantly. Overall, the present experiments show that harman apparently influences 5-HT systems in the brain by its action in inhibiting MAO-A. This property is likely responsible also for the harman-induced increase of 5-HT in the hippocampus of the rats.
Adell
A
A
Department of Pharmacology, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
Biggs
T A
TA
Myers
R D
RD
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D001831:Body Temperature / Q000187:drug effects*; D001923:Brain Chemistry / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D010134:Fenclonine / Q000494:pharmacology; D006247:Harmine / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid / Q000494:pharmacology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006897:Hydroxyindoleacetic Acid / Q000134:cerebrospinal fluid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009498:Neurotoxins / Q000134:cerebrospinal fluid / Q000494:pharmacology*; D010869:Pindolol / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000134:cerebrospinal fluid / Q000378:metabolism*; D018490:Serotonin Agents / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D009498:Neurotoxins; D018490:Serotonin Agents; D012701:Serotonin; D006247:Harmine; D006897:Hydroxyindoleacetic Acid; C005010:harman; D010869:Pindolol; D010134:Fenclonine