Behavioral effects of 5-methoxy-N,N-dimethyltryptamine and dose-dependent antagonism by BC-105
The discriminative effects of 5-methoxy-N,N-dimethyltryptamine (5-OMeDMT) were studied in rats trained to discriminate 1.5 mg/kg or 3.0 mg/kg 5-OMeDMT from saline. A series of antagonist and generalization tests revealed that (1) antagonism of the 5-OMeDMT stimulus response by the presumed serotonin antagonist BC-105 depended on the dose of 5-OMeDMT, (2) the 5-OMe DMT stimulus generalized to LSD, and (3) like 5-OMeDMT, antagonism of the LSD generalization response by BC-105 depended on the dose of LSD. In a second study, with rats responding under a variable-interval (VI) 15-s schedule of reinforcement, doses of 1.0–3.0 mg/kg 5-OMeDMT significantly decreased response rate. Furthermore, the decrease in responding produced by the administration of 1.5 mg/kg (but not by 3.0 mg/kg) 5-OMeDMT was blocked by BC-105. This dosedependent antagonism was of particular interest since the 1.5 mg/kg and 3.0 mg/kg dose of 5-O-MeDMT had essentially the same effect on responding when given alone. The results of both studies emphasize the importance of 5-OMeDMT dose in antagonism experiments.
Key words5-OMeDMT Discriminative stimulus LSD Hallucinogens BC-105 Operant responding Serotonin
Unable to display preview. Download preview PDF.
- DeMontigny C, Aghajanian GK (1977) Preferential action of 5-methoxytryptamine and 5-methoxydimethyltryptamine on presynaptic serotonin receptors: A comparative iontophoretic study with LSD and serotonin. Neuropharmacology 16:811–818Google Scholar
- Freedman DX, Halaris AE (1978) Monoamines and the biochemical mode of action of LSD at synapses. In: Lipton MA, Di Mascio A, Kilam KF (eds) Psychopharmacology: A generation of progress. Raven, New York, pp 347–359Google Scholar
- Fuxe K, Holmstedt B, Johnson G (1972) Effects of 5-methoxy-N,N-dimethyltryptamine on central monoamine neurons. Eur J Pharmacol 19:25–34Google Scholar
- Glennon RA, Rosecrans JA, Young R (1981) Behavioral properties of psychoactive phenylisopropylamines in rats. Eur J Pharmacol 76:353–360Google Scholar
- Glennon RA, Rosecrans JA, Young R, Gaines J (1979) Hallucinogens as discriminative stimuli, Generalization of DOM to a 5-methoxy-N,N-dimethyltryptamine stimulus. Life Sci 24:993–998Google Scholar
- GlennOn RA, Young R, Rosecrans JA, Kallman MJ (1980) Hallucinogenic agents as discriminative stimuli: A correlation with serotonin receptor affinities. Psychopharmacology 68:155–158Google Scholar
- Kantor RE, Dudlettes SD, Shulgin A (1980) 5-Methoxy-α-methyltryptamine (α-0-dimethylserotonin): A hallucinogenic homologue of serotonin. Biol Psychiatry 15:349–352Google Scholar
- Mosko SS, Jacobs BL (1979) Electrophysiological evidence against negative neuronal feedback from the forebrain controlling midbrain raphe unit activity. Brain Res 119:291–303Google Scholar
- Rosecrans JA, Glennon RA (1979) Drug-induced cues in studying mechanisms of drug action. Neuropharmacology 18:981–989Google Scholar
- Young R, Rosecrans JA, Glennon RA (1982) Comparative discriminative stimulus effects of 5-methoxy-N,N-dimethyltryptamine and LSD. Life Sci 30:2057–2062Google Scholar