Convergence and divergence in the neurochemical regulation of prepulse inhibition of startle and N40 suppression in rats.

Prepulse inhibition of startle ('PPI'), a cross-species measure of sensorimotor gating, is impaired in schizophrenia patients. Suppression of P50 event-related potentials (ERPs) in response to the second of two clicks ('P50 gating') is also impaired in schizophrenia. Suppression of N40 ERPs to the second of two clicks ('N40 gating') is thought by some to be a rat homolog of human P50 gating.

Prepulse inhibition of perceived stimulus intensity: paradigm assessment.

In 1939, Helen Peak reported that the presentation of paired acoustic stimuli, separated by 177ms, resulted in a 25% reduction in the perceived intensity of the second stimulus. After 65 years, this form of prepulse inhibition of perceived stimulus intensity (PPIPSI) remains relatively less developed, compared to technically and analytically complex "gating" measures, e.g.

Intact visual latent inhibition in schizophrenia patients in a within-subject paradigm.

People are normally slower to learn a CS-UCS association if they first experience the CS without the UCS. This normal slowing, termed "latent inhibition" (LI), is reported by some to be absent in schizophrenia patients. Our previous studies detected generalized learning deficits but not LI deficits in schizophrenia patients, using between-subject auditory and visual LI paradigms.

Heritable differences in the dopaminergic regulation of sensorimotor gating. II. Temporal, pharmacologic and generational analyses of apomorphine effects on prepulse inhibition.

Rationale And Objectives: The disruption of prepulse inhibition (PPI) of startle in rats by dopamine agonists has been used in a predictive model for antipsychotics, and more recently, to study the neural basis of strain differences in dopaminergic function. We have previously reported that Sprague-Dawley (SDH) and Long Evans (LEH) rats differed in their sensitivity to the PPI-disruptive effects of the D(1)/D(2) agonist apomorphine (APO) in two distinct ways: 1) compared to LEH rats, SDH rats were more sensitive to the ability of APO to disrupt PPI with relatively long prepulse intervals (60-120 ms), and 2) APO enhanced PPI in LEH rats with 10-30 ms prepulse intervals, but this effect was limited to 10 ms prepulse intervals in SDH rats.

Methods: In the present study, we replicated this temporal profile in SDH versus LEH rats, assessed the role of D(1) versus D(2) substrates in the two components of this strain difference, and assessed the heritability of these temporally distinct processes.

Heritable differences in the dopaminergic regulation of sensorimotor gating. I. Apomorphine effects on startle gating in albino and hooded outbred rat strains and their F1 and N2 progeny.

Sensorimotor gating, measured by prepulse inhibition (PPI) of the startle reflex, is reduced in schizophrenia patients and in rats treated with dopamine (DA) agonists. Strain and substrain differences in the sensitivity to the PPI-disruptive effects of DA agonists may provide insight into the basis for human population differences in sensorimotor gating. We have reported greater sensitivity to the PPI disruptive effects of the D(1)/D(2) agonist apomorphine in Harlan Sprague-Dawley (SDH) versus Long Evans (LEH) rats.

Weak prepulses inhibit but do not elicit startle in rats and humans.

Background: Inhibition of startle by weak prestimuli is called prepulse inhibition (PPI). It has recently been reported that 10- to 20-dB prepulses trigger eye-blink motor activity and PPI in normal human subjects. Motor activity after prepulses correlated negatively with PPI in four of nine possible conditions.

Sensitivity to drug effects on prepulse inhibition in inbred and outbred rat strains.

Genetic differences in the neurochemical regulation of PPI in rats may help clarify the neural basis of inherited PPI differences in neuropsychiatric disorders. We reported and characterized substantial heritable differences in sensitivity to PPI-disruptive effects of DA agonists in outbred Sprague Dawley (SDH) versus Long-Evans (LEH) rats. Other strains might yield large group separations and facilitate studies of the neural basis for these strain differences; inbred strains might also allow us to map genes associated with differential PPI sensitivity.

Amphetamine effects on prepulse inhibition across-species: replication and parametric extension.

Despite the similarities of prepulse inhibition (PPI) of the startle reflex and its apparent neural regulation in rodents and humans, it has been difficult to demonstrate cross-species homology in the sensitivity of PPI to pharmacologic challenges. PPI is disrupted in rats by the indirect dopamine (DA) agonist amphetamine, and while studies in humans have suggested similar effects of amphetamine, these effects have been limited to populations characterized by smoking status and specific personality features. In the context of a study assessing the time course of several DA agonist effects on physiological variables, we failed to detect PPI-disruptive effects of amphetamine in a small group of normal males.

Dopamine agonists disrupt visual latent inhibition in normal males using a within-subject paradigm.

Latent inhibition (LI) is the delayed learning of an association when the conditioned stimulus has previously been experienced out of the context of that association. LI can be measured across species and has been used to understand the neurobiology of schizophrenia, since some reports suggest that schizophrenia patients exhibit LI deficits. One challenge of LI studies in humans has resulted from the fact that LI paradigms have almost uniformly involved between-subject comparisons.

Effects of amantadine and bromocriptine on startle and sensorimotor gating: parametric studies and cross-species comparisons.

Background: We recently reported that prepulse inhibition (PPI) in humans was increased by the dopamine (DA) agonist/ N-methyl- D-aspartate (NMDA) antagonist amantadine (200 mg), but was not significantly altered by the DA agonist bromocriptine (1.25-2.5 mg).

Dopamine agonist effects on startle and sensorimotor gating in normal male subjects: time course studies.

Rationale: Prepulse inhibition (PPI) of startle is a measure of sensorimotor gating that is deficient in schizophrenia and in rodents treated with dopamine (DA) agonists. Reduced PPI is reported in normal humans treated with direct or indirect DA agonists. To facilitate future studies, we assessed the time course of DA agonist effects on PPI in humans, for both direct (bromocriptine: 1.