The glycine/NMDA receptor antagonist, L-701,324 reverses isolation-induced deficits in prepulse inhibition in the rat.
Previous studies have demonstrated that the glycine/NMDA receptor antagonist, L-701,324 (7-chloro-4-hydroxy-3(3-phenoxy)phenyl-2(H)quinolone) blocks the activation of mesolimbic dopamine systems induced following psychostimulant administration in the rat (Bristow et al. 1994). In the present study, pretreatment with L-701,324 also reversed the deficit in prepulse inhibition (PPI) observed in rats reared in social isolation after weaning. Given that PPI is also attenuated in schizophrenic patients and that isolation rearing induces both neurochemical and behavioural abnormalities suggestive of a physiologically induced state of dopaminergic hyperactivity, these results suggest that blockade of the glycine/NMDA receptor may offer a new strategy for the development of novel antipsychotic agents.
Bristow
L J
LJ
Sharp and Dohme Research Laboratories, Neuroscience Research Centre, Harlow, Essex, UK.
Landon
L
L
Saywell
K L
KL
Tricklebank
M D
MD
D000161:Acoustic Stimulation; D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D018009:Receptors, Glycine / Q000037:antagonists & inhibitors*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013216:Reflex, Startle / Q000187:drug effects*; D012934:Social Isolation
D015363:Quinolones; D018009:Receptors, Glycine; D016194:Receptors, N-Methyl-D-Aspartate; C094635:L 701324