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Psychopharmacology (2004) 176: 296304DOI 10.1007/s00213-004-1892-9ORIGINAL INVESTIGATIONWalter Adriani . Monica Rea . Marta Baviera .
William Invernizzi . Mirjana Carli .Orlando Ghirardi . Antonio Caprioli .
Giovanni LaviolaAcetyl-L-carnitine reduces impulsive behaviour in adolescent ratsReceived: 17 October 2003 / Accepted: 21 March 2004 / Published online: 8 May 2004
# Springer-Verlag 2004Abstract 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, 3045) 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.Keywords Acetyl-L-carnitine . Methylphenidate .
Impulsivity . Adolescence . SHR . ADHDIntroductionIt is well known from clinical practice that only a portion
of psychiatric patients respond positively to a given drug
therapy, and attention deficit/hyperactivity disorder
(ADHD) actually seems to have heterogeneous origins
(Johansen et al. 2002; Solanto 2002). These considerations
derive from the notion that heterogeneous neurobiological
alterations may lead to similar observed symptoms. For
instance, ADHD is characterized by difficulties in inhibitory control and by impulsivity (Solanto et al. 2001;
Solanto 2002). Several pathogenetic hypotheses have been
proposed, including: (1) dysfunctions in the mesolimbic
system or its inhibitory regulation by the pre-frontal cortex
(PFC) (Johansen et al....