Role of the strychnine-insensitive glycine binding site in the nucleus accumbens and anterodorsal striatum in sensorimotor gating : a behavioral and microdialysis study

• Published in: Psychopharmacologia Vol. 130; no. 2; pp. 131 - 138
• Main Authors: KRETSCHMER, B. D, KOCH, M
• Format: Journal Article
• Language: English
• Published: Berlin Springer 01.03.1997; Springer Nature B.V
• Subjects: Acoustic startle response; Animals; Behavioral psychophysiology; Binding sites; Biogenic Monoamines - metabolism; Biological and medical sciences; Channel gating; Chromatography, High Pressure Liquid; Cycloserine; Dopamine; Dopamine - physiology; Drug delivery; Electrochemistry; Fundamental and applied biological sciences. Psychology; Glutamic acid receptors (ionotropic); Glycine; Glycine Agents - pharmacology; Information processing; Kynurenic Acid - analogs & derivatives; Kynurenic Acid - pharmacology; Male; Mental disorders; Microdialysis; Microinjections; N-Methyl-D-aspartic acid receptors; Neostriatum; Neostriatum - drug effects; Neostriatum - metabolism; Neostriatum - physiology; Nucleus accumbens; Nucleus Accumbens - drug effects; Nucleus Accumbens - metabolism; Nucleus Accumbens - physiology; Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Rats; Rats, Sprague-Dawley; Receptors, Glycine - antagonists & inhibitors; Receptors, Glycine - drug effects; Reflex, Startle - drug effects; Reflexes; Schizophrenia; Sensorimotor gating; Startle response; Strychnine; Strychnine - pharmacology; Rat; Rodentia; Central nervous system; Basal ganglion; Glutamate receptor; Startle reflex; Nucleus accumbens; Vertebrata; Mammalia; Acoustic stimulus; Animal; Glycine receptor; Information processing; NMDA receptor; Gating; Brain (vertebrata)
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s002130050220

This study examined the role of the strychnine-insensitive glycine binding site of the NMDA receptor in prepulse inhibition (PPI) of the acoustic startle response (ASR) in rats. PPI is an operational measure of gating processes which normally lead to a diminished ASR when a startling stimulus is preceded by a weak prepulse. PPI is impaired in schizophrenics and, therefore, experimentally induced PPI deficits in rats can be regarded as a model for gating deficits in schizophrenia. Local administration of 7-chlorokynurenate (7-CLKYN), an antagonist of the strychnine-insensitive glycine site of the NMDA receptor, into the nucleus accumbens reduced PPI. This sensorimotor gating deficit was antagonized by systemic pretreatment of the rats with the glycine site agonist D-cycloserine, indicating that the effect of 7-CLKYN was due to a blockade of the NMDA receptor associated glycine binding site. A similar deficit in PPI was observed after intra-accumbal administration of the competitive NMDA receptor antagonist AP-5. PPI was normal after injecting these drugs into the anterodorsal striatum. The hypothesis that the PPI deficit is accompanied by a change in dopamine release was tested by a neurochemical analysis of the effects of local injection of 7-CLKYN. Microdialysis data showed no increase of accumbal and striatal dopamine release after blockade of the glycine site with 7-CLKYN. Our data demonstrate that the glycine/NMDA receptor in the nucleus accumbens plays a important role in sensorimotor information processing that depends not on a hyperactive dopamine system.