Effects of atomoxetine on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)
- 199 Downloads
The aim of the present study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), which allows a depletion of noradrenergic terminals in a dose-dependent manner, on attention in rats as measured using the five-choice serial-reaction time task (5CSRTT). In addition, we investigated whether the effects of DSP4 treatment can be reversed by atomoxetine. Atomoxetine is a selective noradrenaline reuptake inhibitor and has been shown to be effective in the treatment of attention deficit hyperactivity disorder. Wistar rats were trained in the 5CSRTT and treated with one of the three doses of DSP4 (10, 20 or 50 mg/kg) or saline. Following DSP4 treatment, rats were injected with three doses of atomoxetine (0.1, 0.5 or 1 mg/kg) or saline and tested in the 5CSRTT. The treatment with DSP4 caused a reduction in activity and a decline of performance in parameters related to attention in the 5CSRTT. Whether or not these impairments are due to attention deficits or changes in explorative behaviour and activity remains to be investigated. The treatment with atomoxetine had no beneficial effect on the rats’ performance regardless of the DSP4 treatment. The present findings support the role of noradrenaline in modulating attentional processes and call for future studies regarding the effects of atomoxetine on attention in rats.
KeywordsAtomoxetine Attention deficit hyperactivity disorder N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine DSP4 Rat
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All applicable international, national and/or institutional guidelines for the care and use of animals were followed. All experiments were performed in accordance with the national laws (German law on Protection of Animals) and the principles of laboratory animal care (NIH publication No. 86- 23, revised 1996). The experimental protocol was approved by the District Government of the Oberpfalz/Bavaria (Permit number 54-2531.1-14/07). The rats were handled according to the guidelines of the Federation for European Laboratory Animal Science Associations (FELASA).
- Al Zahrani SS, Al Ruwaitea AS, Ho MY, Bradshaw CM, Szabadi E (1997) Destruction of central noradrenergic neurones with DSP4 impairs the acquisition of temporal discrimination but does not affect memory for duration in a delayed conditional discrimination task. Psychopharmacology 130:166–173CrossRefPubMedGoogle Scholar
- Barkley RA (2006) Attention-deficit hyperactivity disorder: a handbook for diagnosis and treatment, vol 3. Guilford Press, New YorkGoogle Scholar
- Carli M, Robbins TW, Evenden JL, Everitt BJ (1983) Effects of lesions to ascending noradrenergic neurones on performance of a 5-choice serial reaction task in rats; implications for theories of dorsal noradrenergic bundle function based on selective attention and arousal. Behav Brain Res 9:361–380CrossRefPubMedGoogle Scholar
- Deroche V, Marinelli M, Maccari S, Le Moal M, Simon H, Piazza PV (1995) Stress-induced sensitization and glucocorticoids. I. Sensitization of dopamine-dependent locomotor effects of amphetamine and morphine depends on stress-induced corticosterone secretion. J Neurosci 15:7181–7188PubMedGoogle Scholar
- Everitt BJ, Robbins TW, Selden NR (2009) Functions of the locus coeruleus noradrenergic system: a neurobiological and behavioural synthesis. In: Heal DJ, Marsden CA (eds) The pharmacology of noradrenaline in the central nervous system. Oxford University Press, Oxford, pp 349–378Google Scholar
- Roberts AC, De Salvia MA, Wilkinson LS, Collins P, Muir JL, Everitt BJ, Robbins TW (1994) 6-Hydroxydopamine lesions of the prefrontal cortex in monkeys enhance performance on an analog of the Wisconsin Card Sort Test: possible interactions with subcortical dopamine. J Neurosci 14:2531–2544PubMedGoogle Scholar