Prepuberal subchronic methylphenidate and atomoxetine induce different long-term effects on adult behaviour and forebrain dopamine, norepinephrine and serotonin in Naples High-Excitability rats

• Published in: Behavioural brain research Vol. 210; no. 1; pp. 99 - 106
• Main Authors: Ruocco, L.A., Gironi Carnevale, U.A., Treno, C., Sadile, A.G., Melisi, D., Arra, C., Ibba, M., Schirru, C., Carboni, E.
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 26-06-2010; Elsevier
• Subjects: Adrenergic Uptake Inhibitors - administration & dosage; Adrenergic Uptake Inhibitors - pharmacology; Aging; Animals; Atomoxetine; Atomoxetine Hydrochloride; Attention - drug effects; Attention Deficit Disorder with Hyperactivity - drug therapy; Attention Deficit Disorder with Hyperactivity - metabolism; Behavioral psychophysiology; Biological and medical sciences; Central Nervous System Stimulants - administration & dosage; Central Nervous System Stimulants - pharmacology; Disease Models, Animal; Dopamine; Dopamine - metabolism; Fundamental and applied biological sciences. Psychology; Male; Maze Learning - drug effects; Medical sciences; Methylphenidate; Methylphenidate - administration & dosage; Methylphenidate - pharmacology; Naples High-Excitability rats; Neuropharmacology; Norepinephrine; Norepinephrine - metabolism; Pharmacology. Drug treatments; Propylamines - administration & dosage; Propylamines - pharmacology; Prosencephalon - drug effects; Prosencephalon - metabolism; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychology. Psychophysiology; Psychopharmacology; Random Allocation; Rats; Serotonin; Serotonin - metabolism; Time Factors; Naples High-Excitability rats; Norepinephrine; Dopamine; Atomoxetine; Serotonin; Methylphenidate; Subchronic; Rat; Psychotropic; Central nervous system; Reuptake inhibitor; Piperidine derivatives; Adult; Behavior; Human; CNS stimulant; Rodentia; Excitability; Catecholamine; Long term; Prosencephalon; Vertebrata; Mammalia; Animal; Neurotransmitter
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2010.02.020

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.