Behavioral and biochemical evidence for serotonergic actions of tetrahydro-beta-carbolines.
In two groups of rats trained to discriminate LSD (0.1 mg/kg or 0.24 mg/kg) from saline, tetrahydro-beta-carboline (THBC; 1-12 mg/kg as free base) and its derivative 6-methoxy-THBC (1-12 mg/kg as free base) substituted partially for LSD. The substitution of THBC for 0.1 mg/kg of LSD was analyzed further with antagonism tests in 16 animals and was attenuated by the serotonin (5-HT) antagonist BC-105 (pizotifen; 3 mg/kg) but not by the dopamine (DA) antagonist haloperidol (0.1 mg/kg). It was abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (100 mg/kg/day for 3 days). In addition, THBC was found to inhibit 3H-LSD binding to homogenates of rat frontal cortex with an IC50 value of 4 microM which is similar to that previously reported for other 5-HT agonists. These data indicate that THBCs exert potent 5-HT agonist actions. Since THBCs have recently been found in mammalian brain and other tissues, the present results are of interest in relation to a possible role of these substances in endogenous psychosis.
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002243:Carbolines / Q000494:pharmacology*; D004193:Discrimination Learning / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000378:metabolism*
D002243:Carbolines; D007211:Indoles; C002272:6-methoxytryptoline; D012701:Serotonin; C009804:tryptoline; D008238:Lysergic Acid Diethylamide