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Updated: Nov 7, 2025
Habituation and Prepulse Inhibition of Acoustic Startle in Rodents
Published on: September 1, 2011
Disruption of prepulse inhibition is associated with compulsive behavior severity and nucleus accumbens dopamine
Elizabeth E Manning1, Abigail Y Wang1, Linda M Saikali1
1Department of Psychiatry, Translational Neuroscience Program, Center for Neuroscience Program, Center for Neural Basis of Cognition, University of Pittsburgh, BSPII Room 227, 450 Technology Drive, Pittsburgh, PA, 15219, USA.
Abstract:
Obsessive compulsive disorder (OCD) is associated with disruption of sensorimotor gating, which may contribute to difficulties inhibiting intrusive thoughts and compulsive rituals. Neural mechanisms underlying these disturbances are unclear; however, striatal dopamine is implicated in regulation of sensorimotor gating and OCD pathophysiology. The goal of this study was to examine the relationships between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels in Sapap3 knockout mice (KOs), a widely used preclinical model system for OCD research. We found a trend for disruption of sensorimotor gating in Sapap3-KOs using the translational measure prepulse inhibition (PPI); however, there was significant heterogeneity in both PPI and compulsive grooming in KOs. Disruption of PPI was significantly correlated with a more severe compulsive phenotype. In addition, PPI disruption and compulsive grooming severity were associated with reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC). Compulsive grooming progressively worsened in Sapap3-KOs tested longitudinally, but PPI disruption was first detected in high-grooming KOs at 7 months of age. Through detailed characterization of individual differences in OCD-relevant behavioral and neurochemical measures, our findings suggest that NAcC dopamine receptor changes may be involved in disruption of sensorimotor gating and compulsive behavior relevant to OCD.
Insights
Sensorimotor gating deficits in Sapap3 knockout mice correlate with compulsive behaviors. Reduced dopamine D1 and D2/3 receptor density in the nucleus accumbens core may underlie these obsessive-compulsive disorder-relevant disruptions.
Area of Science:
- Neuroscience
- Behavioral Science
- Pharmacology
Background:
- Obsessive compulsive disorder (OCD) involves disrupted sensorimotor gating, impacting thought and behavior inhibition.
- Striatal dopamine plays a role in sensorimotor gating and OCD pathophysiology, but underlying neural mechanisms remain unclear.
Purpose of the Study:
- To investigate the relationship between sensorimotor gating, compulsive behavior, and striatal dopamine receptor levels.
- To utilize Sapap3 knockout mice (KOs) as a preclinical model for OCD research.
Main Methods:
- Assessed sensorimotor gating using prepulse inhibition (PPI) in Sapap3 KOs.
- Quantified compulsive grooming behavior and dopamine D1 and D2/3 receptor density in the nucleus accumbens core (NAcC).
- Employed longitudinal testing to track behavioral changes over time.
Main Results:
- Sapap3 KOs showed a trend for disrupted sensorimotor gating (PPI), with significant individual variability.
- Disrupted PPI significantly correlated with a more severe compulsive grooming phenotype.
- Reduced dopamine D1 and D2/3 receptor density in the NAcC was associated with both PPI disruption and compulsive grooming severity.
- Compulsive grooming worsened longitudinally in KOs, while PPI disruption emerged later in high-grooming individuals.
Conclusions:
- Striatal dopamine receptor alterations, specifically in the NAcC, may contribute to sensorimotor gating deficits.
- These neurochemical changes are implicated in the development of compulsive behaviors relevant to OCD.
- Individual differences in neurobiology are crucial for understanding OCD pathogenesis.
