Naslov
The MDMA influence on the brain serotonin synthesis in rat and dog brains

Autori
Dikšić, Mirko ; Muck-Šeler, Dorotea ; Takahashi, Sho

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Periodicum Biologorum, Vol. 99, Suppl 1 / Vitale, Branko - Zagreb : IGP Štefanović, 1997

Skup
Second Croatian Congress of Pharmacology with International Participation

Mjesto i datum
Rijeka, Hrvatska, 09.09.1997. - 13.09.1997

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Domaća recenzija

Ključne riječi
MDMA; serotonin synthesis; autoradiography; rat brain; dog brain;
(MDMA; serotonin synthesis; autoradiography; rat brain; dog brain)

Sažetak
MDMA (3,4-methylenedioxymethamphetamine; Ecstasy) influence on the brain serotonin (5-HT) synthesis was evaluated in the dog brain by positron emission tomography (PET), and rat brain by autoradiography, and labelled alpha-methyl-L-tryptophan. (11C) and (14C) labelled alpha-MTrp (alpha-methyl-L-tryptophan) were synthesized as described before (Nucl. Med. Biol.22 (1995) 303. PET images were analyzed using linear portion of the curve in which distribution volume was plotted as a function of the exposure time (see details in J. Neurochem.)In rats three sets of experiments were done: 1) injection of 10 mg/kg (i.p.) twice a day and tracer 12 h after the second dose; 2) 5 mg/kg (i.p. ) every 12 h for 4 days and tracer 14 days after the last treatment, and 3) 5 mg/kg (i.p.) every 12 h for 4 days and tracer 14 days after the last treatment. Animals were processed as detailed earlier (J. Cereb. Blood Flow Metab. 10 (1991)1), and the 5-HT synthesis rates were calculated from the tissue and plasma tracer concentrations, and the plasma free Trp (ibid), in some twenty five brain structures. In rats treated for 1 and 2 days with MDMA the regional 5-HT synthesis was significantly increased in all structures. In contrast a significant reduction in seven structures out of 27 structures was found in rats treated for 4 days and assessed 14 days later. In dogs 5 mg/kg (i.v.) of MDMA induced a large increase (about 6 times) some 2 h after MDMA and reduction (about half of the pre-MDMA synthesis) some 6 h after MDMA in the 5-HT synthesis rate. The increase in the synthesis in short periods after MDMA is probably result of compensatory mechanism(s) attempting to replenish pool of the vesicular 5-HT released by MDMA. In dog brain several hours later was reduction in the 5-HT synthesis possibly produced through a feed back inhibitory mechanism of released 5-HT. Data in rats 14 days after the last dose suggest that observed reduction could be in part a result of the MDMA neurotoxicity to the 5-HT neurons. Research supported in part by the NIH and MRC grants.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

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