The N-methyl-D-aspartate antagonist MK-801 protects against serotonin depletions induced by methamphetamine, 3,4-methylenedioxymethamphetamine and p-chloroamphetamine.
The non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocks the ability of D-methamphetamine (MA) to deplete striatal dopamine (DA). We now report that MK-801 attenuates decreases in serotonin (5-HT) concentration induced by MA and two other amphetamine analogues, 3,4-methylenedioxymethamphetamine (MDMA) and p-chloroamphetamine (PCA). Rats were injected with saline (1.0 ml/kg) or MK-801 (0.5, 1.0 or 2.5 mg/kg) followed by either saline (1.0 mg/kg), MA (4, 2 or 1 injection(s); 10.0, 20.0 or 40.0 mg/kg), MDMA (20.0 or 40.0 mg/kg) or PCA (5.0 or 10.0 mg/kg). In some experiments, two injections of MK-801 or saline were used. Seventy-two hours after the last injection rats were sacrificed and concentrations of 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) and DA were determined in hippocampus and striatum. MA caused a depletion of 5-HT to 33% of control in hippocampus and to 50% of control in striatum after the 4 x 10.0 mg/kg dose regimen. When MK-801 (2.5 mg/kg) was co-administered with MA, concentrations of 5-HT did not differ from control levels in either brain region. MDMA depleted 5-HT to approximately 58% of control in hippocampus and 66% of control in striatum at the 40 mg/kg dose.(ABSTRACT TRUNCATED AT 250 WORDS)
University of Chicago, Department of Pharmacological and Physiological Sciences, IL 60637.
G M
GM
Farfel
G L
GL
Vosmer
L S
LS
Seiden
D015104:3,4-Methylenedioxyamphetamine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D010133:p-Chloroamphetamine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D012701:Serotonin; D008694:Methamphetamine; D015104:3,4-Methylenedioxyamphetamine; D016202:N-Methylaspartate; D010133:p-Chloroamphetamine; D016291:Dizocilpine Maleate; D018817:N-Methyl-3,4-methylenedioxyamphetamine