Acetyl-l-carnitine reduces impulsive behaviour in adolescent rats

Adriani, Walter; Rea, Monica; Baviera, Marta; Invernizzi, Roberto William; Carli, Mirjana; Ghirardi, Orlando; Caprioli, Antonio; Laviola, Giovanni

doi:10.1007/s00213-004-1892-9

Cited by 48 publications

(48 citation statements)

References 78 publications

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“…Interestingly, instead of showing an exclusive preference (i.e., 100% for LL), they occasionally chose the alternative SS possibility. This finding, which replicated those of previous experiments in our lab (Adriani, Caprioli, et al, 2003;Adriani, Della Seta, et al, 2003;Adriani & Laviola, 2006;Adriani et al, 2004), indicates that animals express a constant and active patrolling over the two alternative possibilities, as they adaptively probe whether there is any change over time in the outcome associated with nose poking at the nonpreferred hole.…”

Section: Methods Subjectssupporting

confidence: 88%

Home cage testing of delay discounting in rats

Koot

Adriani

Saso

et al. 2009

Behavior Research Methods

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Testing rodents in their home cages has become increasingly popular. Since human intervention, handling, and transport are minimized, behavior can be recorded undisturbed and continuously. Currently existing home cage systems are too complex if only relatively simple operant-learning tests are to be carried out in rats. For that purpose, a new low-cost computer-controlled operant panel was designed, which can be placed inside the home cage. A pilot study was carried out, using an intolerance-to-delay protocol, classically developed for testing behavioral impulsivity. Male adult rats were tested in their home cages, containing the operant panel provided with nose-poking holes. Nose poking in one hole resulted in the immediate delivery of one food pellet (small-soon, SS), whereas nose poking in the other hole delivered five food pellets after a delay (large-late), which was increased progressively each day (0-150 sec). The two daily sessions, spaced 8 h apart, lasted 1 h each, and the time-out after food delivery was 90 sec. A clear-cut shift toward preference for SS, which is considered a classical index of cognitive impulsivity, was shown at the longest delay. It is noteworthy that rats shifted when the delay interval was longer than the mean intertrial interval-that is, when they experienced more than one delay-equivalent odds against discounting (see Adriani & Laviola, 2006). The shortened training (2 days) and testing (5 days) phases, as allowed by prolonged and multiple daily sessions, can be advantageous in testing rodents during selected short phases of development. Current research is focusing on further validation of this and similar protocols

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Section: Methods Subjectssupporting

confidence: 88%

Home cage testing of delay discounting in rats

Koot

Adriani

Saso

et al. 2009

Behavior Research Methods

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“…As expected from previous studies (Adriani et al, , 2004, some rats showed no sign of sensitivity or reactivity to the increasing delay, and continued to prefer the LL option all along the task. A slight decrease towards indifference was evident at the two highest delays, but a clear-cut SS preference was never exhibited (see Table 3).…”

Section: Response Time and Ll Preference In The "Flat" Subgroupsupporting

confidence: 87%

“…Only three male siblings per litter were used in the present experiment, housed in pairs of non-siblings, and tested during the adolescent period (PND 30e44) in the intolerance-to-delay (ID) task. After the first four delay sessions, those rats (ten subjects) demonstrating insensitivity to delay were assigned to the delayinsensitive subgroup and discarded from the drug treatments (Adriani et al, , 2004. The delay-sensitive rats (twenty subjects) were randomly assigned to either challenge with 8-hydroxy-2(di-n-propylamino)tetralin (8-OH-DPAT, Sigma Aldrich, Milan, Italy, at the dose of 0.060 mg/kg) or saline injection for 3 days.…”

Section: Animal Subjects and Treatment Designmentioning

confidence: 99%

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Cognitive impulsivity in animal models: Role of response time and reinforcing rate in delay intolerance with two-choice operant tasks

et al. 2010

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a b s t r a c tImpulsivity, a key symptom of ADHD (attention-deficit hyperactivity disorder), is also common in obsessive-compulsive and addictive disorders. There is rising interest in animal models of inhibitorycontrol impairment. Adolescent rats were tested daily in the intolerance-to-delay (ID) task (session 25 min, timeout 20 s), involving choice between either immediate small amount of food (SS), or larger amount of food after a delay (LL). The mixed 5-HT(1A/7) agonist (8-OH-DPAT, 0 or 0.060 mg/kg i.p.) was administered acutely just before the last three sessions at highest delays. In addition to the classical choice parameter (percent LL preference), the spontaneous waiting (termed response time, RT) occurring between end of a timeout (TO) and next nose-poke was calculated. The pace between consecutive reinforcer deliveries is given by the mean inter-trial interval (mITI, i.e. TO þ RT). Hence, the impact of any given delay may be proportional to this pace and be expressed as delay-equivalent odds, i.e. the extent by which delays are multiples of the mITI. Data revealed that RT/mITI increased sharply from around 15 s/ 35 s to around 30 s/50 s when imposed delay changed from 30 s to 45 s (i.e. odds from 0.91 to 1.06). This suggests that rats adopted a strategy allowing them to keep in pace with perceived reinforcing rate. The increasing delay constraint directly influenced the length of rats' spontaneous waiting (RT) before next decision. For higher delays, with odds >1, rats shifted to a clear-cut SS preference, which is devoid of any exogenous temporal constraint. A challenge with 8-OH-DPAT (0 or 0.060 mg/kg i.p.) decreased impulsive choice but also increased RT. Thus, tapping onto 5-HT(1A/7) receptors slightly enhanced RT/mITI values, possibly reflecting ability of rats to cope with slower reinforcing rates and/or with delay-cancelled reward paces. In summary, delay-induced states of aversion may arise from the innate tendency to rely on a regular rate of reinforcement. Conversely, a drug-enhanced capacity to cope with delay may involve an internal ability to adjust expectancy about such a reinforcing rate.

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“…It is now accepted that these paradoxical findings can be due to differences in experimental procedures (Cardinal et al, 2000), or particularly to a baselinedependent effect (Barbelivien et al, 2008). In our work, where the delay interval was signaled, increased choice for the large reinforcer could be expected for SIL rats, like it would be expected with amphetamine (Cardinal et al, 2000) and methylphenidate (Adriani et al, 2004). However, the slightly enhanced impulsivity of SIL rats shall be discussed in terms of the reduced motivation also found in the novelty seeking test.…”

Section: Impulsivity and Novelty Seekingmentioning

confidence: 48%

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

et al. 2009

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Abstract-Multiple theories have been proposed for sensation seeking and vulnerability to impulse-control disorders [Zuckerman M, Kuhlman DM (2000) Personality and risk-taking: Common biosocial factors. J Pers 68:999 -1029], and many of these rely on a dopamine system deficit. Available animal models reproduce only some behavioral symptoms and seem devoid of construct validity. We used lentivirus tools for over-expressing or silencing the dopamine transporter (DAT) and we evaluated the resulting behavioral profiles in terms of motivation and self-control. Wistar adult rats received stereotaxic inoculation of a lentivirus that allowed localized intra-accumbens delivery of a DAT gene enhancer/ silencer, or the green fluorescent protein, GFP. These animals were studied for intolerance to delay, risk proneness and novelty seeking. As expected, controls shifted their demanding from a large reward toward a small one when the delivery of the former was increasingly delayed (or uncertain). Interestingly, in the absence of general locomotor effects, DAT over-expressing rats showed increased impulsivity (i.e. a more marked shift of demanding from the large/ delayed toward the small/soon reward), and increased risk proneness (i.e. a less marked shift from the large/uncertain toward the small/sure reward), compared with controls. Rats with enhanced or silenced DAT expression did not show any significant preference for a novel environment. In summary, consistent with literature on comorbidity between attentiondeficit/hyperactivity disorder and pathological gambling, we demonstrate that DAT over-expression in rats' nucleus accumbens leads to impulsive and risk prone phenotype. Thus, a reduced dopaminergic tone following altered accumbal DAT function may subserve a sensation-seeker phenotype and the vulnerability to impulse-control disorders.

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Acetyl-l-carnitine reduces impulsive behaviour in adolescent rats

Cited by 48 publications

References 78 publications

Home cage testing of delay discounting in rats

Home cage testing of delay discounting in rats

Cognitive impulsivity in animal models: Role of response time and reinforcing rate in delay intolerance with two-choice operant tasks

Increased impulsive behavior and risk proneness following lentivirus-mediated dopamine transporter over-expression in rats' nucleus accumbens

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