Auditory Event-Related Potentials in Two Rat Models of Attention-Deficit Hyperactivity Disorder: Evidence of Automatic Attention Deficits in Spontaneously Hypertensive Rats but Not in Latrophilin-3 Knockout Rats

This study investigated whether two distinct animal models of ADHD—the Lphn3 knockout (KO) rat and the spontaneously hypertensive rat (SHR)—exhibit deficits in automatic attention. While ADHD is often studied through the lens of voluntary, effortful attention, automatic attention—the involuntary processing of environmental stimuli—is a critical component of arousal and sensory gating. The researchers used a passive auditory paradigm, presenting rats with trains of five tones separated by either short (1 s) or long (5 s) inter-train intervals (ITIs). By measuring auditory event-related potentials (ERPs), specifically the P1, N1, P2, and N2 components, the team sought to determine if these models show impaired neural responses to auditory stimuli, which would indicate dysfunction in bottom-up arousal networks.

The researchers found a clear divergence between the two models. The Lphn3 KO rats showed no significant differences in ERP peak amplitudes compared to their wildtype (WT) controls, suggesting that the null expression of the Lphn3 gene does not lead to deficits in automatic attention. In contrast, the SHRs exhibited significantly reduced P1 and P1-N1 amplitudes compared to their Wistar-Kyoto (WKY) controls. This attenuation was most pronounced following the longer (5 s) ITI, indicating that SHRs fail to show the expected neural recovery or robust response to salient stimuli. The researchers suggest this reflects an inefficiency in bottom-up subcortical arousal networks, likely involving the locus coeruleus-norepinephrine system, rather than a failure of top-down frontal inhibition.

These findings provide important insights into the neurobiological heterogeneity of ADHD. By demonstrating that SHRs exhibit clear deficits in automatic attention while Lphn3 KOs do not, the study highlights that different genetic and physiological models of ADHD may tap into distinct neural pathways. This distinction is crucial for translational research, as it suggests that the efficacy of ADHD medications—which modulate dopamine and norepinephrine—may depend on the specific underlying neurobiological profile of the individual. The study also validates the use of auditory ERPs as a translational tool for bridging preclinical animal research with human clinical findings.