New perspectives from microdialysis studies in freely-moving, spontaneously hypertensive rats on the pharmacology of drugs for the treatment of ADHD

Noise benefit in prepulse inhibition of the acoustic startle reflex

“…Furthermore, HVA was significantly lower in the nucleus accumbens of SH rats compared to Wistar controls. Previously performed microdialysis studies in SH rats show increased basal DA levels in the striatum and the nucleus accumbens shell; however, they also demonstrate substantially larger effects of the DAT inhibitors methylphenidate and amphetamine in SH rats compared to SD and Wistar-Kyoto rats (Heal et al 2008;Carboni et al 2003), which is in agreement with high reuptake activity. Most available data are in support of high DAT activity in SH rats, but there seems to be some regional differences.…”

Lisdexamfetamine and immediate release d-amfetamine – Differences in pharmacokinetic/pharmacodynamic relationships revealed by striatal microdialysis in freely-moving rats with simultaneous determination of plasma drug concentrations and locomotor activity

“…We have also proposed that rapid onset of effect together with magnitude and duration of increases in extracellular concentrations of noradrenaline and dopamine in prefrontal cortex (PFC) and sub-cortical regions, eg striatum, correlates well with the clinical efficacy of ADHD drugs (Heal et al, 2008(Heal et al, , 2009(Heal et al, , 2012. In the current experiments, IR D-amfetamine evoked a rapid and substantial increase of extracellular dopamine in the striatum that exceeded 1000% of basal levels at 30 min and this finding is consistent with data that we and others have reported previously (Zetterström et al, 1986;Kuczenski and Segal, 1997;Heal et al, 2008Heal et al, , 2009Heal et al, , 2012. By comparison, the effect of an equivalent dose of lisdexamfetamine was more gradual in onset taking 75 min to reach its maximum.…”

α2- and β-adrenoceptors involvement in nortriptyline modulation of auditory sustained attention and impulsivity

“…Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterized by impaired behavioral inhibition (Barkley 1997;Brennan and Arnsten 2008), impulsive decision making, impaired working memory with underlying distractibility, and hyperactivity (Arnsten et al 1996;Sagvolden 2006;Brennan and Arnsten 2008;Heal et al 2008) along with severe deficits in executive function (Barkley 1997;Lovejoy et al 1999;Sonuga-Barke 2005). Importantly, patients with ADHD or prefrontal lesions show poor performance in working memory and behavioral inhibition tasks (Arnsten and Li 2005).…”