Selective activation of dopaminergic pathways in the mesocortex by compounds that act at the phencyclidine (PCP) binding site: tentative evidence for PCP recognition sites not coupled to N-methyl-D-aspartate (NMDA) receptors.
Several lines of evidence suggest a tight functional coupling between N-methyl-D-aspartate (NMDA) and phencyclidine (PCP) receptors. The effects of PCP receptor agonists (PCP, dexoxadrol, ketamine and MK-801) and NMDA receptor antagonists, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755) and 3-(2-carboxypiperizin-4-yl)-propyl-1-phosphonic acid (CPP), have been examined on the metabolism of dopamine in the mesocortex, with a view of studying the coupling between these two receptor systems. Phencyclidine receptor agonists selectively increased the metabolism of dopamine in the mesocortex without affecting the metabolism of dopamine in the striatum. N-Methyl-D-aspartate and the competitive antagonists of NMDA receptors did not effect the metabolism of dopamine, neither did the sigma receptor ligands, 1,3-di-(2-tolyl)guanidine (DTG) and rimcazole. Rimcazole also did not affect the increases in the metabolism of dopamine in the mesocortex, seen after MK-801. These data indicate that dopaminergic neurons in the mesocortex are positively modulated by PCP receptors but tentatively suggest that those recognition sites for PCP are not coupled to NMDA receptors.
Rao
T S
TS
Research Department, CIBA-GEIGY Pharmaceuticals Division, Summit, New Jersey 07901.
Kim
H S
HS
Lehmann
J
J
Martin
L L
LL
Wood
P L
PL
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects*; D003986:Dibenzocycloheptenes / Q000494:pharmacology; D016291:Dizocilpine Maleate; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009434:Neural Pathways / Q000502:physiology*; D010875:Pipecolic Acids; D010879:Piperazines; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D017478:Receptors, Phencyclidine; D013237:Stereoisomerism
D002227:Carbazoles; D003986:Dibenzocycloheptenes; D006146:Guanidines; D008024:Ligands; D010875:Pipecolic Acids; D010879:Piperazines; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D015102:3,4-Dihydroxyphenylacetic Acid; C053672:selfotel; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; C034931:rimcazole; C050232:1,3-ditolylguanidine; D004298:Dopamine