The spontaneously hypertensive-rat as an animal model of ADHD: evidence for impulsive and non-impulsive subpopulations

被引:136
作者
Adriani, W
Caprioli, A
Granstrem, O
Carli, M
Laviola, G
机构
[1] Ist Super Sanita, Dept Cell Biol & Neurosci, Behav Pathophysiol Sect, Lab FOS, I-00161 Rome, Italy
[2] Sigma Tau Pharmaceut Co, Behav Pharmacol Lab, Pomezia, Italy
[3] Emory Univ, Dept Chem, Atlanta, GA 30322 USA
[4] IP Pavolov State Med Univ, Dept Neurol & Neurosurg, St Petersburg, Russia
[5] Mario Negri Inst Pharmacol Res, Dept Neurosci, I-20157 Milan, Italy
关键词
impulsivity; spontaneously hypertensive-rat; attention-deficit hyperactivity disorder; cannabinoid; CB1; receptor; rat; DEFICIT HYPERACTIVITY DISORDER; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; CENTRAL 5-HYDROXYTRYPTAMINE DEPLETION; PREFRONTAL CORTEX; NONSELECTIVE ATTENTION; RECEPTOR ANTAGONIST; ANTERIOR FOREBRAIN; NUCLEUS-ACCUMBENS; MESOLIMBIC SYSTEM; RESPONSE CHOICE;
D O I
10.1016/j.neubiorev.2003.08.007
中图分类号
B84 [心理学]; C [社会科学总论]; Q98 [人类学];
学科分类号
03 ; 0303 ; 030303 ; 04 ; 0402 ;
摘要
Attention-deficit hyperactivity disorder (ADHD) is a neuropsychiatric syndrome, affecting human infants and adolescents. Two main behavioural features are reported: (1) impaired attention and (2) an impulsive-hyperactive behavioural trait. The latter has been studied in a series of experiments, using the spontaneously hypertensive-rat (SHR) strain (which is regarded as a validated animal model for ADHD) in operant tasks. Food-restricted SHRs and their Wistar-Kyoto (WKY) controls were tested during adolescence (i.e. post-natal days 30-45), in operant chambers provided with two nose-poking holes. Nose-poking in one hole (H I) resulted in the immediate delivery of a small amount of food, whereas nose-poking in the other hole (H5) delivered a larger amount of food after a delay, which was increased progressively each day (0100 s). As expected. all animals showed a shift in preference from the large (H5) to the immediate (HI) reinforcer as the delay length increased. Impulsivity can be measured by the steepness of this preference-delay curve. The two strains differed in home-cage circadian activity, SHRs being more active than WKYs at several time-points. During the test for impulsivity, inter-individual differences were completely absent in the WKY strain, whereas a huge inter-individual variability was evident for SHRs. On the basis of the median value of average hole-preference, we found an 'impulsive' SHR subgroup, with a very quick shift towards the HI hole, and a flat-slope ('non-impulsive') SHR subgroup, with little or no shift. The impulsive subpopulation also presented reduced noradrenaline levels in both cingulated and medial-frontal cortex, as well as reduced serotonin turnover in the latter. Also, cannabinoid CB I receptor density resulted significantly lower in the prefrontal cortex of impulsive SHRs, when compared to both the non-impulsive subgroup and control WKYs. Interestingly, acute administration of a cannabinoid agonist (WIN 55.212, 2 mg/kg s.c.) normalized the impulsive behavioural profile, without any effect on WKY rats. Thus, two distinct subpopulations, differing for impulsive behaviour and specific neurochemical parameters, were evidenced within adolescent SHRs. These results support the notion that a reduced cortical density of cannabinoid CB I receptors is associated with enhanced impulsivity. This behavioural trait can be positively modulated by administration of a cannabinoid agonist. Present results confirm and extend previous literature, indicating that adolescent SHRs represent a suitable animal model for the preclinical investigation of the early-onset ADHD syndrome. (C) 2003 Elsevier Ltd. All fights reserved.
引用
收藏
页码:639 / 651
页数:13
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