Effect of MK-801 on the decrease in tryptophan hydroxylase induced by methamphetamine and its methylenedioxy analog.
The role of N-methyl-D-aspartate (NMDA) receptors in the decrease in neostriatal tryptophan hydroxylase (TPH) activity induced by repeated high doses of methamphetamine or 3,4-methylenedioxymethamphetamine (MDMA) was evaluated. Rats received 4 injections of methamphetamine (15 mg/kg) or MDMA (10 mg/kg) at 6 h intervals, and were killed 18-20 h after the last administration. These treatments with methamphetamine or MDMA reduced neostriatal TPH activity to 26 and 34% of control, respectively. Coadministration of MK-801 (2.5 mg/kg) significantly attenuated the methamphetamine-induced decrease in TPH activity (66% of control), but did not alter the effect of MDMA. This study suggests that excitatory amino acids may participate in the methamphetamine-induced decline in central TPH activity, and that the mechanism by which MDMA and methamphetamine decreases TPH activity may differ.
Johnson
M
M
Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Hanson
G R
GR
Gibb
J W
JW
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives / Q000494:pharmacology*; D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology*; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism; D014365:Tryptophan Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D000662:Amphetamines; D000927:Anticonvulsants; D003986:Dibenzocycloheptenes; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D016291:Dizocilpine Maleate; D014365:Tryptophan Hydroxylase; D018817:N-Methyl-3,4-methylenedioxyamphetamine