Changes in prepulse inhibition after local administration of NMDA receptor ligands in the core region of the rat nucleus accumbens.
The dopamine and glutamate hypotheses are two pharmacological models for schizophrenia. In the present investigations, the prepulse inhibition paradigm was used to evaluate the role of the nucleus accumbens core region in both models. Prepulse inhibition is known to be decreased in schizophrenics, when compared with control patients, and in rats after systemic injection of dopamine receptor agonists and non-competitive antagonists of the NMDA receptor. In the present study injection of dopamine in the rat nucleus accumbens core region also decreased prepulse inhibition. Injections of NMDA decreased, whereas a low dose of the competitive NMDA receptor antagonist (+/-)-2-amino-5-phosphonopentanoic acid (AP-5) and the non-competitive NMDA receptor antagonist (5R,10S)-(+)-5-methyl-10,11-dihydroxy-5H-dibenzo[a,d]cyclohepten-5 ,10-imine hydrogen maleate (MK-801) increased prepulse inhibition. The results indicate an involvement of the accumbens core in mediating the systemic effects on prepulse inhibition of dopamine receptor agonists but not of non-competitive NMDA receptor antagonists.
Reijmers
L G
LG
Department of Neuropharmacology, Organon International B.V., Oss, Netherlands.
Vanderheyden
P M
PM
Peeters
B W
BW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006624:Hippocampus / Q000187:drug effects; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology*; D010622:Phencyclidine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*
D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D010622:Phencyclidine; D004298:Dopamine