The psychostimulant methylphenidate and the non-stimulant atomoxetine are two approved
drugs for attention-deficit hyperactivity disorder (ADHD) therapy. The aim of this
study was to investigate the long-term effects of prepuberal subchronic methylphenidate
and atomoxetine on adult behaviour and the forebrain neurotransmitter and metabolite
content of Naples High-Excitability (NHE) rats, a genetic model for the mesocortical
variant of ADHD. Male NHE rats were given a daily intraperitoneal injection (1.0mg/kg)
of methylphenidate, atomoxetine or vehicle from postnatal day 29 to 42. At postnatal
day 70-75, rats were exposed to spatial novelty in the Làt and radial (Olton) mazes.
Behavioural analysis for indices of horizontal, vertical, non-selective (NSA) and
selective spatial attention (SSA) indicated that only methylphenidate significantly
reduced horizontal activity to a different extent, i.e., 39 and 16% respectively.
Moreover methylphenidate increased NSA as assessed by higher leaning duration. The
high-performance liquid chromatography (HPLC) tissue content assessment of dopamine,
norepinephrine, serotonin and relative metabolites in the prefrontal cortex (PFC),
cortical motor area (MC), dorsal striatum (DS), ventral striatum (VS), hippocampus
and mesencephalon indicated that methylphenidate decreased (i) dopamine, DOPAC, norepinephrine,
MHPG, 5-HT and 5-HIAA in the PFC, (ii) dopamine, DOPAC, HVA, serotonin, 5-HIAA in
the DS, (iii) dopamine, DOPAC, HVA and MHPG (but increased norepinephrine) in the
VS and (iv) norepinephrine, MHPG, serotonin and 5-HIAA in the hippocampus. Atomoxetine
increased dopamine and decreased MHPG in the PFC. Like methylphenidate, atomoxetine
decreased dopamine, DOPAC, HVA, serotonin and 5-HIAA in the DS, but decreased MHPG
in the VS. These results suggest that methylphenidate determined long-term effects
on behavioural and neurochemical parameters, whereas atomoxetine affected only the
latter.