The ventral pallidum mediates disruption of prepulse inhibition of the acoustic startle response induced by dopamine agonists, but not by NMDA antagonists.
Prepulse inhibition (PPI) of the acoustic startle response is observed when the startling noise pulse is preceded by a weak, non-startling stimulus. PPI has been considered as a measure for sensorimotor gating mechanisms. Disruption of PPI can be found in schizophrenic patients as well as after blockade of NMDA receptors or stimulation of dopamine receptors in rats. The neuronal circuitry which regulates PPI consists of cortico-limbic brain structures where the nucleus accumbens (NAC) plays a key role. The NAC exerts its modulating effects on PPI by way of a projection from the ventral pallidum (VP) to the pedunculopontine tegmental nucleus (PPTg). We recently postulated that the reduction of PPI by intra-NAC infusion of glycine-site NMDA antagonists is not mediated by the VP. We tested here this hypothesis in rats with excitotoxic lesions of the VP which were systemically treated with apomorphine or MK-801 or received intraNAC infusions of dopamine or the glycine-site NMDA antagonist 7-chlorokynurenic acid. Lesioned rats showed a marked deficit in PPI after MK-801 and 7-chlorokynurenate treatment but not after apomorphine or dopamine injection, in contrast to sham-lesioned controls showing deficits in PPI under all conditions. These data provide behavioral evidence for the existence of a pathway which does not include the VP for the mediation of sensorimotor gating deficits. We propose that a direct connection between the NAC and PPTg may be responsible for the effects of NMDA/glycine receptor blockade, whereas the VP is an indispensable relay for the disruptive effects on PPI exerted by the NAC dopamine system.
Department of Neuropharmacology, University of Tübingen, Mohlstr. 54/1, 72074 Tübingen, Germany. beate.kretschmer@uni-tubingen.de
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D000161:Acoustic Stimulation; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D005917:Globus Pallidus / Q000502:physiology*; D007267:Injections; D007736:Kynurenic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors*; D009433:Neural Inhibition / Q000502:physiology*; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology*
D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D016291:Dizocilpine Maleate; D007736:Kynurenic Acid; D001058:Apomorphine; C057013:7-chlorokynurenic acid