Effects of atomoxetine, desipramine, d-amphetamine and methylphenidate on impulsivity in juvenile rats, measured in a T-maze procedure.
ABSTRACT Impulsivity is a core symptom of Attention Deficit/Hyperactivity Disorder (ADHD). In the present study, we assessed the effects of two stimulants, methylphenidate and d-amphetamine and of two non stimulant noradrenaline reuptake inhibitors, atomoxetine and desipramine, on the tolerance to delay of reward, taken as an index of impulsivity, in juvenile Wistar rats. Animals were trained in a T-maze to choose between a small-and-immediate reward and a large-but-30s-delayed reward. The effects of drugs were studied on the performance of animals at 30-40 day of age. Methylphenidate (3mg/kg), atomoxetine (1mg/kg), d-amphetamine (1 and 2mg/kg) and desipramine (8 and 16mg/kg) increased the number of choices of the large-but-delayed reward, i.e. decreased impulsivity. Given that these drugs are commonly prescribed in ADHD, these data indicate that the T-maze procedure in juvenile animals may be suitable for testing the therapeutic potential of drugs intended to the treatment of ADHD in children.
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ABSTRACT: Atomoxetine (ATX) is a commonly used non-stimulant treatment for Attention Deficit Hyperactivity Disorder (ADHD). It primarily acts to increase noradrenalin levels; however, at higher doses it can increase dopamine levels. To date there has been no investigations into the effects of orally-administered ATX in the most commonly used model of ADHD, the spontaneously hypertensive rat (SHR). The aim of this study was to describe the effects of doses thought to be selective (0.15mg/kg) and non-selective (0.3mg/kg) for noradrenalin on behavioural measures in the SHR. Firstly, we examined the effects of acute and chronic ATX on locomotor activity including sensitization and cross-sensitization to amphetamine. Secondly, we measured drug effects on impulsivity using a T-maze delay discounting paradigm. We found no effect of ATX on locomotor activity and no evidence for sensitization or cross-sensitization. Furthermore, there were no differences in T-maze performance, indicating no effects on impulsivity at these doses. The absence of behavioural sensitization supports previous claims of superior safety relative to psychostimulants for the doses administered. There was also no effect on impulsivity; however, we suggest that was confounded by stress specific to SHRs. Implications for future studies, behavioural assessment of SHRs and their use as a model of ADHD are discussed.Behavioural brain research 12/2012; · 3.22 Impact Factor
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ABSTRACT: Lisdexamfetamine dimesylate (LDX) is a novel prodrug of d-amphetamine that is currently used for the treatment of attention-deficit/hyperactivity disorder in children aged ≥6 years and adults. LDX is enzymatically cleaved to form d-amphetamine following contact with red blood cells which reduces the rate of appearance and magnitude of d-amphetamine concentration in the blood and hence the brain when compared with immediate-release d-amphetamine at equi-molar doses. Thus, the increase of striatal dopamine efflux and subsequent increase of locomotor activity following d-amphetamine is less prominent and slower to attain maximal effect following an equimolar dose of LDX. Furthermore, unlike d-amphetamine, the pharmacodynamic effects of LDX are independent of the route of administration underlining the requirement to be hydrolysed by contact with red blood cells. It is conceivable that these pharmacokinetic and pharmacodynamic differences may impact the psychostimulant properties of LDX in the clinic. This article reviews the preclinical pharmacokinetics, pharmacology, and toxicology of LDX.Neuropharmacology 03/2014; · 4.82 Impact Factor