Decreased Prepulse Inhibition Research Articles

Neonatal cytomegalovirus exposure decreases prepulse inhibition in adult rats: Implications for schizophrenia

The goal of these studies was to determine whether neonatal viral exposure leads to a deficit in information processing in adulthood. To accomplish this, rats were infected neonatally with rat cytomegalovirus, and acoustic startle responses were measured when rats were 120 days old. Acoustic startle was elicited by using a 118-decibel (dB) white noise alone or after a prepulse 10 dB above background (65 dB); responses were measured after an injection of saline or the dopamine agonist apomorphine. Response amplitudes after the pulse alone were not significantly altered by either viral exposure or apomorphine. Responses of animals exposed to the prepulse before the pulse were approximately 10% of that after the pulse alone and did not differ between control or virus-exposed animals injected with saline. Animals injected with apomorphine exhibited a greater startle response than animals injected with saline, and control and virus-exposed rats injected with apomorphine differed in the magnitude of their responses. Apomorphine attenuated responses after the prepulse, and virus-exposed animals exhibited more than twice the attenuation than non-virus-exposed animals. Analysis of prepulse inhibition, calculated from the acoustic startle data, indicated that although viral exposure alone did not significantly affect information processing, when virus-injected rats were exposed to apomorphine, a significant 38% decrease in prepulse inhibition was apparent. Findings demonstrate that rats infected neonatally with rat cytomegalovirus exhibit a deficit in sensorimotor gating upon dopamine stimulation, supporting a possible link between viral infection and schizophrenia.

The phenotypic characteristics of heterozygous reeler mouse.

Histological and behavioral traits are associated with reelin (Reln) haplo-insufficiency in heterozygous reeler mouse (rl+/-). These phenotypic traits are an approximately 50% decrease of brain Reln mRNA and Reln protein, an accumulation of nicotinamide-adenine dinucleotide phosphate-diaphorase (NADPH-d)-positive neurons in subcortical white matter, an age-dependent decrease in prepulse inhibition of startle (PPI), and neophobic behavior on the elevated plus-maze. Possible analogies between these rl+/- phenotypic traits and signs of psychosis vulnerability are discussed.

Competitive NMDA receptor antagonists disrupt prepulse inhibition without reduction of startle amplitude in a dopamine receptor-independent manner in mice

Prepulse inhibition is thought to reflect the operation of the sensorimotor gating system in the brain, and is reduced in schizophrenic patients and in animals treated with non-competitive NMDA receptor antagonists such as phencyclidine and (+)-5-methyl-10,11-dihydro-5 H-dibenzo[ a, d]cyclohepten-5,10-imine ((+)-MK-801). Previously, we reported that a competitive NMDA receptor antagonist, cis-4-phosphonomethyl-2-piperidine-carboxylate hydrochloride (CGS 19755), also disrupts prepulse inhibition concomitantly with a marked reduction of startle amplitude elicited by pulse alone in rats. In the present study, the effect of NMDA receptor antagonists on prepulse inhibition was tested in mice. In addition, involvement of the dopaminergic system in CGS 19755-induced disruption of prepulse inhibition was examined. When CGS 19755 was subcutaneously administered at 40 and 80 mg/kg, prepulse inhibition was disrupted without any change in the startle amplitude elicited by pulse alone. Intracerebroventricularly administered CGS 19755 disrupted prepulse inhibition at dosages of 0.1 and 0.2 μg/mouse. The same dosages of R-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid ( R-CPP), another competitive NMDA receptor antagonist, also decreased prepulse inhibition, while its less active enantiomer, S-CPP, did not affect prepulse inhibition at 0.2 μg/mouse (i.c.v.). A typical neuroleptic, haloperidol, did not significantly improve CGS 19755 (40 mg/kg s.c.)-induced disruption of prepulse inhibition. These results suggest that the disruption of prepulse inhibition by CGS 19755 and R-CPP is NMDA receptor-mediated and dopamine receptor-independent.

Smoking cues decrease prepulse inhibition of the startle response and increase subjective craving in humans.

Smoking cues decrease prepulse inhibition of the startle response and increase subjective craving in humans.

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 (5 R,10 S)-(+)-5-methyl-10,11-dihydroxy-5 H-dibenzo[ a,d]cycloheten-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.

Acoustic prepulses can facilitate the startle reflex in rats: Discrepancy between rat and human data resolved

Small changes in the sensory environment, called prepulses, prior to a startle-eliciting stimulus can inhibit or facilitate the startle reaction. Previous studies reported that at large intervals between prepulse and startle stimulus the prepulse facilitates the startle reaction, possibly by means of an orienting response. This was, however, only observed in humans and not in rats, and was consequently proposed to measure unique brain functions. In the present study with rats, the prepulse intensity was decreased from 85 to 81 dB, which resulted in decreased prepulse inhibition. Prepulse facilitation was now observed at large intervals (> 800 ms), which suggests that this facilitation was masked by inhibition in previous studies. These results solve the discrepancy between rat and human data and indicate that similar mechanisms are involved.