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

Background/Objectives: Variations of the latrophilin-3 (Lphn3) gene have been associated with attention-deficit hyperactivity disorder (ADHD). To explore the functional influence of this gene, Lphn3 knockout (KO) rats were generated and have thus far demonstrated deficits in ADHD-relevant phenotypes, including working memory, impulsivity, and hyperactivity. However, inattention remains unexplored. Methods: We assessed automatic attention in Lphn3 KO (n = 19) and their control line (wildtype/WT, n = 20) through use of the following auditory event-related potentials (ERPs): P1, N1, P2, and N2. We also extended this exploratory study by comparing these same ERPs in spontaneously hypertensive rats (SHRs, n = 16), the most commonly studied animal model of ADHD, to their control line (Wistar–Kyoto/WKY, n = 20). Electroencephalograms (EEG) were recorded using subdermal needle electrodes at frontocentral sites while freely moving rats were presented with five-tone trains (50 ms tones, 400 ms tone onset asynchronies) with varying short (1 s) and long (5 s) inter-train intervals. Peak amplitudes and latencies were analyzed using GLM-mixed ANOVAs to assess differences across genotypes (KO vs. WTs) and strains (SHRs vs. WKYs). Results: The KOs did not demonstrate any significant differences in peak amplitudes relative to the WT controls, suggesting that the null expression of Lphn3 does not result in the development of inefficiencies in automatic attention. However, the SHRs exhibited significantly reduced peak P1 (and peak-to-peak P1–N1) values relative to the WKYs. These attenuations likely reflect inefficiencies in bottom-up arousal networks that are necessary for efficient automatic processing. Conclusions: Distinct findings between these animal models likely reflect differing alterations in dopamine and noradrenaline neurotransmission that may underlie ADHD-relevant phenotypes.