A central component of Attention-Deficit Hyperactivity Disorder (ADHD) is increased distractibility, which is linked to the superior colliculus (SC) in a range of species, including humans. Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate the main symptoms of ADHD, including distractibility. In the present study we have provided a systematic characterization of the SC in the most commonly used and well-validated animal model of ADHD, the spontaneously hypertensive rat (SHR). We examined collicular-dependent orienting behavior, local field potential (LFP) and multiunit responses to visual stimuli in the anesthetized rat and morphological measures in the SHR in comparison to the Wistar Kyoto (WKY) and Wistar (WIS). We found that SHRs remain responsive to a repeated visual stimulus for more presentations than control strains and have a longer response duration. In addition, LFP and multiunit activity within the visually responsive superficial layers of the SC showed the SHR to have a hyper-responsive SC relative to control strains, which could not be explained by altered functioning of the retinocollicular pathway. Finally, examination of collicular volume, neuron and glia densities and glia:neuron ratio revealed that the SHR had a reduced ratio relative to the WKY which could explain the increased responsiveness. In conclusion, this study demonstrates strain-specific changes in the functioning and structure of the SC in the SHR, providing convergent evidence that the SC might be dysfunctional in ADHD.

A central component of Attention Deficit Hyperactivity Disorder (ADHD) is increased distractibility in response to visual and auditory stimuli, which is linked to the superior colliculus (SC). Furthermore, there is now mounting evidence of altered collicular functioning in ADHD and it is proposed that a hyper-responsive SC could mediate symptoms of ADHD, including distractibility. In the present study we conducted a systematic characterisation of the intermediate and deep layers of the SC in the most commonly used and well-validated model of ADHD, the spontaneously hypertensive rat (SHR), building on prior work showing increased distractible behaviour in this strain using visual distractors. We examined collicular-dependent orienting behaviour, local field potential (LFP) and multiunit activity (MUA) in response to auditory stimuli in the anaesthetised rat, and morphological measures, in the SHR in comparison to the Wistar Kyoto (WKY) and Wistar (WIS). We found no evidence of increased distractibility in the behavioural data but suggest that this may arise due to cochlear hearing loss in the SHR. Furthermore, the electrophysiology data indicate that the SC in the SHR may still be hyper-responsive, normalising the amplitude of auditory responses that would otherwise be reduced due to the hearing impairment. The morphological measures of collicular volume, cell density and ratios did not indicate this potential hyper-responsiveness had a basis at the structural level examined. These findings have implications for future use of the SHR in auditory processing studies and may represent a limitation to the validity of this animal model.

BackgroundThe spontaneously hypertensive rat is thought to show good validity as a model of attention deficit hyperactivity disorder, in part because of impaired delayed reinforcement behaviour, corresponding to the dynamic developmental theory of the disorder. However, some previous studies may have been confounded use of fluid reward. Therefore, the objective of this study was to assess the spontaneously hypertensive rat and two comparison strains (Wistar and Wistar Kyoto) using a non-delayed food reinforcement paradigm in an attempt to advance knowledge of basic learnt behaviour in this strain, without potentially confounding reward sensitivity, which could impact on motivation to learn. Rats were trained on a fixed ratio 1 two choice discrimination schedule, extinction, reacquisition and reversal. We also tested non-reinforced spontaneous alternation to facilitate data interpretation.ResultsThe spontaneously hypertensive rat displayed slower shaping and reduced on task activity during task acquisition, contrasting with previous results which indicate either enhanced responding and an impairment only when a delay is used; we suggest several reasons for this. In line with previous work, the same strain exhibited poor extinguishing of behaviour but were not impaired to the same extent on reversal of the discrimination. Finally, non-reinforced alternations on a Y-maze were also reduced in the spontaneously hypertensive rat.ConclusionsIn sum, the spontaneously hypertensive rat appear to show poor response inhibition in reinforced and non-reinforced contexts. However, impaired response inhibition was reduced during reversal when an opposite response produced food reward alongside presentation of the conditioned stimulus. We discuss the possibility of enhanced attribution of incentive salience to cues in this strain and highlight several points of caution for researchers conducting behavioural assessments using the spontaneously hypertensive rat and their associated comparison strains.Electronic supplementary materialThe online version of this article (10.1186/s13104-017-2857-5) contains supplementary material, which is available to authorized users.

No abstract