Abstract
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.
This is a preview of subscription content, log in via an institution to check access.
References
Bristow LJ, Hutson PH, Thorn L, Trickleband MD (1993) The glycine/NMDA receptor antagonist,R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents. Br J Pharmacol 108: 1156–1163
Bristow LJ, Young L, Tricklebank MD (1994) The glycine/NMDA receptor antagonist, L-701,324, selectively modulates mesolimbic dopamine systems in rat. Behav Pharmacol 5 [Supplement 1]: 41–42
Geyer MA, Wilkinson LS, Humby T, Robbins TW (1993) Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol Psychiatry 34: 361–372
Grace AA (1991) Phasic versus tonic dopamine release and the modulation of dopamine system responsitivity: a hypothesis for the etiology of schizophrenia. Neuroscience 41: 1–24
Hutson PH, Bristow LJ, Thorn L, Tricklebank MD (1991)R-(+)-HA-966, a glycine/NMDA receptor antagonist, selectively blocks the activation of the mesolimbic dopamine system by amphetamine. Br J Pharmacol 103: 2037–2044
Johnson SW, Seutin V, North RA (1992) Burst firing in dopamine neurones induced byN-methyl-D-aspartate: role of electrogenic sodium pump. Science 258: 665–667
Jones GH, Hernandez TD, Kendall DA, Marsden CA, Robbins TW (1992) Dopaminergic and serotonergic function following isolation rearing in rats: study of behavioural responses and postmortem and in vivo neurochemistry. Pharmacol Biochem Behav 43: 17–35
Keith VA, Mansbach RS, Geyer MA (1991) Failure of haloperidol to block the effects of phencyclidine and dizocilpine on prepulse inhibition of startle. Biol Psychiatry 30: 557–566
Mansbach RS, Geyer MA (1989) Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat. Neuropsychopharmacology 2: 299–308
Rowley M, Leeson PD, Stevenson GI, Moseley AM, Stansfield I, Sanderson I, Robinson L, Baker R, Kemp JA, Marshall GR, Foster AC, Grimwood S, Tricklebank MD, Saywell KL (1993) 3-Acetyl-4-hydroxyquinolin-2(H)-ones. Systemically active anticonvulsants acting by antagonism at the glycine site of theN-methyl-D-aspartate receptor complex. J Med Chem 36: 3386–3396
Swerdlow NR, Braff DL, Taaid N, Geyer MA (1994) Assessing the validity of an animal model of deficient sensorimotor gating in schizophrenic patients. Arch Gen Psychiatry 51: 139–154
Wan FJ, Swerdlow NR (1993) Intra-accumbens infusion of quinpirole impairs sensorimotor gating of acoustic startle in rats. Psychopharmacology 113: 103–109
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Bristow, L.J., Landon, L., Saywell, K.L. et al. The glycine/NMDA receptor antagonist, L-701,324 reverses isolation-induced deficits in prepulse inhibition in the rat. Psychopharmacology 118, 230–232 (1995). https://doi.org/10.1007/BF02245847
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF02245847