Biomaterial Database

The N-methyl-D-aspartate antagonist MK-801 protects against serotonin depletions induced by methamphetamine, 3,4-methylenedioxymethamphetamine and p-chloroamphetamine. 1992

G M Farfel, and G L Vosmer, and L S Seiden

University of Chicago, Department of Pharmacological and Physiological Sciences, IL 60637.

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)

UI	MeSH Term	Description	Entries
D008297	Male		Males
D008694	Methamphetamine	A central nervous system stimulant and sympathomimetic with actions and uses similar to DEXTROAMPHETAMINE. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed.	Deoxyephedrine,Desoxyephedrine,Desoxyn,Madrine,Metamfetamine,Methamphetamine Hydrochloride,Methylamphetamine,N-Methylamphetamine,Hydrochloride, Methamphetamine,N Methylamphetamine
D010133	p-Chloroamphetamine	Chlorinated analog of AMPHETAMINE. Potent neurotoxin that causes release and eventually depletion of serotonin in the CNS. It is used as a research tool.	p-Chloramphetamine,para-Chloroamphetamine,LY-121860,Ly-123362,Parachloroamphetamine,LY 121860,LY121860,Ly 123362,Ly123362,p Chloramphetamine,p Chloroamphetamine,para Chloroamphetamine
D003342	Corpus Striatum	Striped GRAY MATTER and WHITE MATTER consisting of the NEOSTRIATUM and paleostriatum (GLOBUS PALLIDUS). It is located in front of and lateral to the THALAMUS in each cerebral hemisphere. The gray substance is made up of the CAUDATE NUCLEUS and the lentiform nucleus (the latter consisting of the GLOBUS PALLIDUS and PUTAMEN). The WHITE MATTER is the INTERNAL CAPSULE.	Lenticular Nucleus,Lentiform Nucleus,Lentiform Nuclei,Nucleus Lentiformis,Lentiformis, Nucleus,Nuclei, Lentiform,Nucleus, Lenticular,Nucleus, Lentiform,Striatum, Corpus
D006624	Hippocampus	A curved elevation of GRAY MATTER extending the entire length of the floor of the TEMPORAL HORN of the LATERAL VENTRICLE (see also TEMPORAL LOBE). The hippocampus proper, subiculum, and DENTATE GYRUS constitute the hippocampal formation. Sometimes authors include the ENTORHINAL CORTEX in the hippocampal formation.	Ammon Horn,Cornu Ammonis,Hippocampal Formation,Subiculum,Ammon's Horn,Hippocampus Proper,Ammons Horn,Formation, Hippocampal,Formations, Hippocampal,Hippocampal Formations,Hippocampus Propers,Horn, Ammon,Horn, Ammon's,Proper, Hippocampus,Propers, Hippocampus,Subiculums
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012701	Serotonin	A biochemical messenger and regulator, synthesized from the essential amino acid L-TRYPTOPHAN. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Multiple receptor families (RECEPTORS, SEROTONIN) explain the broad physiological actions and distribution of this biochemical mediator.	5-HT,5-Hydroxytryptamine,3-(2-Aminoethyl)-1H-indol-5-ol,Enteramine,Hippophaine,Hydroxytryptamine,5 Hydroxytryptamine
D015104	3,4-Methylenedioxyamphetamine	An amphetamine derivative that inhibits uptake of catecholamine neurotransmitters. It is a hallucinogen. It is less toxic than its methylated derivative but in sufficient doses may still destroy serotonergic neurons and has been used for that purpose experimentally.	3,4 Methylenedioxyamphetamine
D016202	N-Methylaspartate	An amino acid that, as the D-isomer, is the defining agonist for the NMDA receptor subtype of glutamate receptors (RECEPTORS, NMDA).	N-Methyl-D-aspartate,NMDA,N-Methyl-D-aspartic Acid,Acid, N-Methyl-D-aspartic,N Methyl D aspartate,N Methyl D aspartic Acid,N Methylaspartate
D016291	Dizocilpine Maleate	A potent noncompetitive antagonist of the NMDA receptor (RECEPTORS, N-METHYL-D-ASPARTATE) used mainly as a research tool. The drug has been considered for the wide variety of neurodegenerative conditions or disorders in which NMDA receptors may play an important role. Its use has been primarily limited to animal and tissue experiments because of its psychotropic effects.	Dizocilpine,MK-801,MK 801,MK801