Effects of phencyclidine, MK-801 and 1,3-di(2-tolyl)guanidine on non-dopaminergic midbrain neurons.
The effects of i.v. administration of the noncompetitive NMDA receptor antagonists, phencyclidine and MK-801, and the sigma receptor ligand, 1,3-di(2-tolyl)guanidine (DTG), on the firing rates of non-dopaminergic mid brain neurons were evaluated in chloral hydrate-anesthetized rats. Phencyclidine and MK-801 inhibited the activity of putative gamma-aminobutyric acid (GABA)-containing interneurons identified by their response to foot-pinch. DTG did not significantly alter neuronal activity. These results suggest that the reported excitatory effects of non-competitive NMDA receptor antagonists on dopamine neuronal activity are due, in part, to disinhibition secondary to the inhibition of interneuron activity.
Zhang
J
J
Department of Psychiatry, Wayne State University School of Medicine, Detroit, MI.
Chiodo
L A
LA
Freeman
A S
AS
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006146:Guanidines / Q000494:pharmacology*; D007275:Injections, Intravenous; D008297:Male; D008636:Mesencephalon / Q000166:cytology / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010622:Phencyclidine / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017480:Receptors, sigma / Q000187:drug effects
D006146:Guanidines; D017480:Receptors, sigma; D016291:Dizocilpine Maleate; D010622:Phencyclidine; C050232:1,3-ditolylguanidine