Ca2+ channel blockade prevents lysergic acid diethylamide-induced changes in dopamine and serotonin metabolism.
To investigate the effect of a single and multiple administration of lysergic acid diethylamide (LSD) on cerebral metabolism of dopamine and serotonin, male Wistar rats were treated with low and high doses (0.1 and 2.0 mg/kg i.p.) of LSD and the levels of dopamine, 3,4-dihydroxyphenylacetic acid, homovanillic acid, 3-methoxytyramine, serotonin and 5-hydroxyindoleacetic acid were assayed by HPLC in the nucleus accumbens, striatum and frontal cortex. Some rats received nifedipine, 5 mg/kg i.p., before each injection of LSD to assess the effect of a Ca2+ channel blockade. High-dose LSD treatment (8 x 2 mg/kg per day) caused a strong stimulation of dopamine metabolism in the nucleus accumbens and striatum, and serotonin metabolism in the nucleus accumbens: the changes were observed 24 (but not 1 h) after the last dose. The changes induced by the low-dose treatment (8 x 0.1 mg/kg per day) had a different pattern, suggesting the release of dopamine from vesicles to cytoplasm. Co-administration of nifedipine completely prevented the LSD-induced biochemical changes. The results suggest that Ca2+ channel blocking agents may prevent development of some behavioral consequences of chronically used LSD.
Antkiewicz-Michaluk
L
L
Institute of Pharmacology, Polish Academy of Sciences, Krakow.
Románska
I
I
Vetulani
J
J
D000818:Animals; D001921:Brain / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D006212:Hallucinations / Q000378:metabolism / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014793:Visual Cortex / Q000187:drug effects
D002121:Calcium Channel Blockers; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D008238:Lysergic Acid Diethylamide; D009543:Nifedipine; D004298:Dopamine