Behavior of hypertensive and hyperactive rat strains: Hyperactivity is not unitarily determined

Sagvolden, Terje; Hendley, Edith D.; Knardahl, Stein

doi:10.1016/0031-9384(92)90432-2

Cited by 148 publications

(99 citation statements)

References 23 publications

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“…Moreover, the strain that appeared to be most impaired in terms of PPI performance was WKY, as PPI in WKY animals was lower than that in WKHA and WIS, at least at the low levels of prepulse intensity. In the open field test, saline-treated WKHA rats were indeed more active in the open field exploration test in comparison with the inbred control WKY strain, as has been previously reported (Sagvolden et al 1992). The activity of WKHA rats was, however, lower than that observed in the outbred Wistar control strain and also that of Lewis rats (results not shown).…”

supporting

confidence: 82%

“…WKHA display marked locomotor hyperactivity and hyperreactivity to stress when compared with WKY. The activity score obtained with WKHA in an exploration test in a novel environment is much higher than the score observed in the WKY strain (Sagvolden et al 1992). Moreover, the WKHA also seems to display "attentional problems" when compared with WKY (Sagvolden et al 1992).…”

mentioning

confidence: 62%

“…The activity score obtained with WKHA in an exploration test in a novel environment is much higher than the score observed in the WKY strain (Sagvolden et al 1992). Moreover, the WKHA also seems to display "attentional problems" when compared with WKY (Sagvolden et al 1992). Although these characteristics are reminiscent of those observed in children diagnosed with attention deficit disorder (ADHD), the utility of this strain as a potential model of ADHD has not received extensive experimental attention.…”

mentioning

confidence: 92%

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Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Drolet

Proulx

Pearson

et al. 2002

Neuropsychopharmacology

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WKHA rats constitute a recombinant inbred rat strain derived by phenotypic selection of the progeny of hybrid F2 crosses between SHR and WKY rats. WKHA are normotensive and show some features of hyperactivity and of hyper-reactivity to stress, but their utility as model of attention deficit/hyperactivity disorder (ADHD) has not yetWistar-Kyoto-derived Hyperactive (WKHA) rats constitute an inbred strain that has been derived from the progeny of hybrid Wistar-Kyoto (WKY)/ Spontaneously Hypertensive Rats (SHR) F2 crosses. The WKHA rats were developed initially in 1980 by Hendley and associates in the attempt to remove a prominent behavioral abnormality (hyperactivity) from the hypertensive trait of SHR that had been fixed in this strain during intensive inbreeding (Hendley and Ohlsson 1991;Hendley 2000). Using cross-breeding of SHR with WKY followed by recombinant selected inbreeding, Hendley and Ohlsson (1991) (Deschepper et al. 1997). WKHA display marked locomotor hyperactivity and hyperreactivity to stress when compared with WKY. The activity score obtained with WKHA in an exploration test in a novel environment is much higher than the score observed in the WKY strain (Sagvolden et al. 1992). Moreover, the WKHA also seems to display "attentional problems" when compared with WKY (Sagvolden et al. 1992). Although these characteristics are reminiscent of those observed in children diagnosed with attention deficit disorder (ADHD), the utility of this strain as a potential model of ADHD has not received extensive experimental attention.Accordingly, the present study was conducted to assess the face validity of the WKHA strain as a model of ADHD. To do so, we compared the performance of WKHA to both WKY (genetic control) and Wistar (outbred control) strains in two behavioral tests. First, we measured activity levels of the three strains in an exploration test in a novel environment. Second, we examined the behavior of the three strains in the prepulse inhibition (PPI) test of the acoustic startle reflex. This test assesses sensorimotor gating, or the extent to which a weak acoustic stimulus draws cognitive processing away from a more pronounced acoustic stimulus (Ralph et al. 1999;Wood et al. 1998). Although there is considerable debate as to whether PPI reflects the operation of an attentional (as opposed to a preattentional) mechanism, it is clear that PPI is involved in stimulus selection or stimulus filtering, a process that appears to be aberrant in ADHD (Ralph et al. 1999). Moreover, some evidence also exists for a deficit in sensorimotor gating in a sub-population of ADHD children (Castellanos et al. 1996). A third reason justifying our use of the PPI test is that, like locomotor activity, sensorimotor gating is modulated by central dopaminergic substrates (Swerdlow et al. 1994), and there is extensive clinical evidence implicating alterations in dopaminergic function in the pathophysiology of ADHD (Pliszka et al. 1996).We also examined the extent to which the performances of the three strains in both the locom...

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supporting

confidence: 82%

mentioning

confidence: 62%

mentioning

confidence: 92%

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Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Drolet

Proulx

Pearson

et al. 2002

Neuropsychopharmacology

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“…2,3,8,11,12,18,[27][28][29][30][31][32][33][34][35][36][37][38][39][40] On the other hand, it has been suggested that the behavioral changes observed in SHR reflect a decreased ability to deal with threatening situations. 18,22,25,28,32 Therefore, the use of the autoshaping test as a nonthreatening behavioral task is completely justified. 2,3,5,7,9,11,41 …”

Section: Cognitive Deficits Induced By Hypertension and Agingmentioning

confidence: 99%

Spontaneously Hypertensive Rats

Meneses

Hong

1998

Hypertension

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Abstract-Spontaneously hypertensive rats (SHR) of 3 to 12 months of age learned and retrieved less information than normotensive Wistar-Kyoto rats (WKY), although no difference was found with animals from 18 and 24 months of age. The combined influence of hypertension and aging had an additive detrimental effect on cognitive functions. Notwithstanding these deficiencies in learning and memory, SHR have seldom been used as a model in the screening of drugs with therapeutic potential for treatment of disorders of cognitive processes. Moreover, the calcium channel blocker nimodipine has beneficial effects on learning in both aged and hypertensive animals and humans. However, no attempt has been made to investigate whether nimodipine can reverse the additive deleterious effects of aging and hypertension in the same subject. We recently reported that deteriorated animals (middle-aged and/or hypertensive) chronically treated with nimodipine (via osmotic minipumps) exhibit higher learning scores. This information indicates that nimodipine can reverse the impairing effects of either aging or hypertension on learning; the presence of the two conditions, however, produces a severe impairment that can be partially reversed by this drug. Therefore, we propose that mature and middle-aged SHR represent a model for the screening of potentially useful drugs in the treatment of learning disorders, probably associated with hypertension and/or aging. Nevertheless, it must be remembered that the SHR is a genetic model and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to hypertension per se. (Hypertension. 1998;31:968-972.)Key Words: rats, inbred SHR Ⅲ learning Ⅲ memory Ⅲ aging Ⅲ pharmacology Ⅲ models A great expansion of experimental research began with the development of rat strains with genetically inherited hypertension. The SHR offers specific and uniform genetic predisposition, 1 thus allowing the study of the causes, mechanisms, and pathology of hypertension, as well as its behavioral consequences, and the comparison of the efficacy of proposed therapeutic interventions in relation to existing clinical treatments. Moreover, central neurohormonal mechanisms constitute the dominating trigger influence in SHR 1 and provide a model of hypertension that allows the study of the combined influence of both aging and hypertension on cognitive and physical functions on different developmental stages.2,3 Notwithstanding, the SHR is a genetic model, and the appearance of neural disturbances could be a parallel genetic phenomenon and not necessarily or exclusively related to the elevated blood pressure per se. Normal aging also produces a slow decline in neuron population, tissue distensibility, basal metabolic rate, and oxygen consumption, thus affecting cardiovascular performance. The aim of the present work was to present evidence obtained in our laboratory supporting the idea that the SHR is a suitable behavioral model to test drugs with potential therapeutic us...

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“…Consistent with such a scenario, breeding studies have provided evidence that a component of the behavioural profile of the SHR cosegegrates with the D 1A signalling defect. 40 A second rat strain considered to be a useful behavioural model of ADHD is the Naples High Excitability (NHE) rat. 41 In a recent study it was shown that D 1A expression in the PFC is abnormally low in the NHE rat.…”

Section: Introductionmentioning

confidence: 99%

Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder

et al. 2003

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Attention-deficit/hyperactivity disorder (ADHD) has a strong genetic basis, and evidence from human and animal studies suggests the dopamine receptor D1 gene, DRD1, to be a good candidate for involvement. Here, we tested for linkage of DRD1 to ADHD by examining the inheritance of four biallelic DRD1 polymorphisms [D1P.5 (-1251HaeIII), D1P.6 (À800HaeIII), D1.1 (À48DdeI) and D1.7 ( þ 1403Bsp1286I)] in a sample of 156 ADHD families. Owing to linkage disequilibrium between alleles at the four markers, only three haplotypes are common in our sample. Using the transmission/disequilibrium test (TDT), we observed a strong bias for transmission of Haplotype 3 (1.1.1.2) from heterozygous parents to their affected children (P¼0.008). Furthermore, using quantitative trait TDT analyses, we found significant and positive relationships between Haplotype 3 transmission and the inattentive symptoms, but not the hyperactive/impulsive symptoms, of ADHD. These findings support the proposed involvement of DRD1 in ADHD, and implicate Haplotype 3, in particular, as containing a potential risk factor for the inattentive symptom dimension of the disorder. Since none of the four marker alleles comprising Haplotype 3 is predicted to alter DRD1 function, we hypothesize that a functional DRD1 variant, conferring susceptibility to ADHD, is on this haplotype. To search for such a variant we screened the DRD1 coding region, by sequencing, focusing on the children who showed preferential transmission of Haplotype 3. DNA from 41 children was analysed, and no sequence variations were identified, indicating that the putative DRD1 risk variant for ADHD resides outside of the coding region of the gene.

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Behavior of hypertensive and hyperactive rat strains: Hyperactivity is not unitarily determined

Cited by 148 publications

References 23 publications

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Comparisons of Behavioral and Neurochemical Characteristics between WKY, WKHA, and Wistar Rat Strains

Spontaneously Hypertensive Rats

Linkage of the dopamine receptor D1 gene to attention-deficit/hyperactivity disorder

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