Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)

Abstract

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats' performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats.

Theory of visual attention (TVA) applied to rats performing the 5-choice serial reaction time task: differential effects of dopaminergic and noradrenergic manipulations

“…That AMPH and MPH did not affect accuracy is generally consistent with previous 5CSRTT studies in healthy rodents treated with comparable (low to moderate) doses of MPH (Navarra et al 2008;Milstein et al 2010;Fernando et al 2012;Pattij et al 2012;Hauser et al 2017) and AMPH (Cole and Robbins 1987;Harrison et al 1999;Van Gaalen et al 2006;Loos et al 2010;Balachandran et al 2018;Higgins et al 2020). Although a few studies have reported these drugs to improve accuracy during increased task demand and/or in low-attention rats (Koffarnus and Katz 2011;Robinson 2012;Caballero-Puntiverio et al 2017;Toschi et al 2021) as well as in high-impulsive rats (Caprioli et al 2015), we did not observe any effects on accuracy in LA rats.…”