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Acetyl-l-carnitine reduces impulsive behaviour in adolescent rats

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Abstract

The attention deficit/hyperactivity disorder (ADHD) can affect human infants and adolescents. One important feature of this disorder is behavioural impulsivity. This study assessed the ability of chronic acetyl-l-carnitine (ALC, saline or 100 mg/kg SC, plus 50 mg/kg orally) to reduce impulsivity in a validated animal model for ADHD. Food-restricted rats were tested during adolescence (postnatal days, pnd, 30–45) in operant chambers with two nose-poking holes, one delivering one food pellet immediately, and the other five pellets after a delay. Delay length was increased over days (from 0 to 80 s). Individual differences in the preference-delay curve emerged, with the identification of two distinct subpopulations, i.e. one with a nearly horizontal curve and another with a very steep (“impulsive”) slope. The impulsivity profile was slightly but consistently reduced by chronic ALC administration. Consistent results were also obtained with methylphenidate (MPH, saline or 3 mg/kg IP twice daily). Impulsive rats exhibited a lower metabolite/serotonin (5HIAA/5HT) ratio in the medial frontal cortex (MFC) and lower noradrenaline (NA) levels in the MFC and cingulate cortex (CC) when compared with the other subgroup. The ALC treatment increased NA levels in the CC and the 5HIAA/5HT ratio in both CC and MFC. Present data suggest that ALC, a drug devoid of psychostimulant properties, may have some beneficial effects in the treatment of ADHD children.

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Acknowledgements

This research was supported by the Research Project on “Hypoxic-ischemic brain damage in the newborn” (0AN/F grant to G.L.), Ministry of Health, Italy; by the Young Investigator Award “Behavioural handicap at developing ages” (CNRG00A0A8 grant to W.A.), Agenzia2000, CNR, Italy; and by Sigma-Tau SpA, Pomezia, Italy. We wish to thank Marco Sbragi, who developed the computer software for the operant chambers.

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  1. Behavioural Neuroscience Section, Dept. Cell Biology & Neurosciences, Istituto Superiore di Sanita’, viale Regina Elena 299, 00161, Rome, Italy

    Walter Adriani, Monica Rea & Giovanni Laviola

  2. Department of Neuroscience, “Mario Negri” Institute for Pharmacological Research, Milano, Italy

    Marta Baviera, William Invernizzi & Mirjana Carli

  3. Central and Peripheral Nervous System, “Sigma-Tau” SpA, Pomezia, Italy

    Orlando Ghirardi & Antonio Caprioli

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  1. Walter Adriani
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  2. Monica Rea
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  3. Marta Baviera
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  4. William Invernizzi
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  8. Giovanni Laviola
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Correspondence to Giovanni Laviola.

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Adriani, W., Rea, M., Baviera, M. et al. Acetyl-l-carnitine reduces impulsive behaviour in adolescent rats. Psychopharmacology 176, 296–304 (2004). https://doi.org/10.1007/s00213-004-1892-9

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