Comprehensive behavioral profiling in male spontaneously hypertensive rats: latent trait mapping supports a valid...

Attention-deficit/hyperactivity disorder (ADHD) is a heterogeneous neurodevelopmental disorder marked by inattention, impulsivity, and hyperactivity. Although the spontaneously hypertensive rat (SHR) is widely used to model ADHD, intra-strain behavioral heterogeneity and its neurobiological relevance remain insufficiently defined. We conducted a comprehensive multidomain behavioral assessment of male adolescent SHR and Wistar-Kyoto (WKY) rats spanning locomotion/exploration, anxiety- and risk-related behavior, compulsive-like activity, cognition, and sensorimotor gating. Across tasks, SHR rats exhibited increased impulsive and repetitive exploratory behaviors, context-dependent alterations in anxiety-related measures, reduced spontaneous alternation, and impaired prepulse inhibition. Exploratory factor analysis of 26 behavioral variables identified five interpretable latent dimensions, including exploratory-attentional engagement and impulsivity/disinhibition, and revealed substantial heterogeneity within the SHR population. Using WKY-referenced factor-score deviation, SHR were stratified into normative-range and combined-deviant subtypes. The combined-deviant subtype exhibited convergent circuit-level alterations, including reduced parvalbumin (PV)/glutamate decarboxylase 67 (GAD67)-associated inhibitory features and decreased synaptic marker signals in prelimbic and infralimbic medial prefrontal cortex, together with increased dopamine transporter expression (DAT) in the striatum without changes in tyrosine hydroxylase (TH). Complementary principal axis factoring, bootstrap resampling, and split-sample analyses supported the robustness of the factor structure. These findings link multidimensional behavioral subtypes in SHR to distinct prefrontal-striatal signatures, strengthening the translational utility of SHR-based ADHD research.