Spontaneously Hypertensive Rat substrains show differences in model traits for addiction risk and cocaine self-administration: Implications for a novel rat reduced complexity cross.

Forward genetic mapping of F2 crosses between closely related substrains of inbred rodents - referred to as a reduced complexity cross (RCC) - is a relatively new strategy for accelerating the pace of gene discovery for complex traits, such as drug addiction. RCCs to date were generated in mice, but rats are thought to be optimal for addiction genetic studies. Based on past literature, one inbred Spontaneously Hypertensive Rat substrain, SHR/NCrl, is predicted to exhibit a distinct behavioral profile as it relates to cocaine self-administration traits relative to another substrain, SHR/NHsd. Direct substrain comparisons are a necessary first step before implementing an RCC. We evaluated model traits for cocaine addiction risk and cocaine self-administration behaviors using a longitudinal within-subjects design. Impulsive-like and compulsive-like traits were greater in SHR/NCrl than SHR/NHsd, as were reactivity to sucrose reward, sensitivity to acute psychostimulant effects of cocaine, and cocaine use studied under fixed-ratio and tandem schedules of cocaine self-administration. Compulsive-like behavior correlated with the acute psychostimulant effects of cocaine, which in turn correlated with cocaine taking under the tandem schedule. Compulsive-like behavior also was the best predictor of cocaine seeking responses. Heritability estimates indicated that 22 %-40 % of the variances for the above phenotypes can be explained by additive genetic factors, providing sufficient genetic variance to conduct genetic mapping in F2 crosses of SHR/NCrl and SHR/NHsd. These results provide compelling support for using an RCC approach in SHR substrains to uncover candidate genes and variants that are of relevance to cocaine use disorders.

Impulsivity in spontaneously hypertensive rats: Within-subjects comparison of sensitivity to delay and to amount of reinforcement.

Previous research has shown that spontaneously hypertensive rats (SHR) display higher levels of impulsive choice behavior, which is accompanied by a higher sensitivity to the delay of reinforcement, and by a normal sensitivity to the amount of reinforcement. Because those results were based on three different samples of subjects, in the present report we evaluated these three processes in the same individuals. SHR and WIS rats were exposed to concurrent-chains schedules in which the terminal links were manipulated to assess impulsivity, sensitivity to delay, and sensitivity to amount. For exploring impulsivity, a terminal link was associated with a small reinforcer (1 pellet) delivered after a short delay (2s) while the other terminal link was associated with a larger reinforcer (4 pellets) delivered after a longer delay (28s). For assessing sensitivity to delay, both alternatives delivered the same amount of reinforcement (1 pellet) and the only difference between them was in the delay before reinforcement delivery (2s vs 28s). For assessing sensitivity to amount, both alternatives were associated with the same delay (15s), but the alternatives differed in the amount of reinforcement (1 vs 4 pellets). In addition to replicating previously observed effects within-subjects, we were interested in analyzing different aspects of the regularity of rats' actions in the choice task. The results confirmed that previous findings were not a consequence of between-group differences: SHR were more impulsive and more sensitive to delay, while their sensitivity to amount was normal. Analyses of response regularity indicated that SHR subjects were more periodic in their responses to levers and in their feeder entries, had a higher number of short-duration bouts of responding, and made a substantially higher number of switches between the alternatives. We discuss the potential implications of these findings for the possible behavioral mechanisms driving the increased sensitivity to delay in SHR.

Comparison of the validity of the use of the spontaneously hypertensive rat as a model of attention deficit hyperactivity disorder in males and females.

The spontaneously hypertensive rat (SHR) is a commonly used and well-studied rodent model of attention deficit hyperactivity disorder (ADHD). Sex differences in the cognitive symptoms of ADHD are reported. However, the female SHR rat is much less studied than its male counterpart. The goal of the current study was to assess the validity of the SHR rodent model of ADHD by examining attentional performance, inhibitory control, and hyperactivity in both male and female SHR rats. Adult SHR and control Wistar-Kyoto rats were trained on the 5-choice serial reaction time task, a self-paced test of attention and inhibitory control. This task requires animals to identify the location of a brief light stimulus among five possible locations under several challenging conditions. Analyses of percent correct revealed that attentional performance in SHR females was not significantly different from control females, whereas attentional performance in SHR males was significantly different from control males. Analyses of the number of premature responses revealed that SHR rats made more inhibitory control errors than did control rats and that this decrease in inhibitory control was present in both SHR males and females. Analyses of activity in the open field revealed that SHR rats were more hyperactive than were control rats and that this increased hyperactivity was present in both SHR males and females. The current findings have implications for the study of sex differences in ADHD and for the use of SHR rats as a model of ADHD in females.

Cross-fostering differentially affects ADHD-related behaviors in spontaneously hypertensive rats.

Although both genetic and non-genetic factors are known to contribute to the occurrence of Attention-Deficit Hyperactivity/Disorder (ADHD), little is known about how they impact specific symptoms. We used a cross-fostering approach with an established animal model of ADHD, the Spontaneously Hypertensive Rat strain (SHR), to test the influence of genotype and maternal behavior on ADHD-related behaviors. SHRs and their normo-active genetic relative, Wistar Kyoto rats (WKY), were cross-fostered to an unfamiliar dam of either the same or different strain. Behavioral testing took place when the rats reached adulthood. Locomotor hyperactivity was completely dependent on the strain of the offspring. In contrast, social behavior was primarily determined by the strain of the mother, while attentional orienting behavior was influenced by both the strain of the offspring and the strain of the dam. Anxiety-related behavior was influenced by an interaction between offspring and dam strain.

Intra-orbitofrontal cortex injection of haloperidol removes the beneficial effect of methylphenidate on reversal learning of spontaneously hypertensive rats in an attentional set-shifting task.

Numerous studies suggest that attention-deficit/hyperactivity disorder (ADHD) is caused by deficits in catecholaminergic systems. Furthermore, dysfunctions of prefrontal cortex can impair inhibitory controls of ADHD patients, resulting in their impulsive behaviors. Researchers also find that rats with lesions in the orbitofrontal cortex show deficits in the reversal learning of attentional set-shifting task (ASST), a behavioral test frequently used in human studies to asses the inhibition system. However, the role of orbitofrontal dopamine system in the mechanism responsible for the dysfunctions of inhibitory controls in ADHD patients and animal models remains unknown. In the present study, we manipulated orbitofrontal dopamine activities of spontaneously hypertensive rats (SHR), a widely used ADHD animal model, through intra-peritoneal injection of methylphenidate (MPH) and central infusion of haloperidol, and observed their performances in ASST. The results show that juvenile SHRs learned slower than Wistar controls in the first and second reversal learnings of ASST. The deficits could be removed by intra-peritoneal injections of MPH. Furthermore, central infusions of haloperidol in the orbitofrontal cortex blocked the effects of MPH. In conclusions, dopamine activity in orbitofrontal cortex might play a crucial role in the neural mechanism of reversal learning deficits in this animal model of ADHD.

Responding in a test of decision-making under risk is under moderate genetic control in the rat.

BACKGROUND: Risk-taking, measured with laboratory tasks such as the Balloon Analog Risk Task (BART), is associated with real-life manifestations of risky behaviors, which may be an important component of inherited liability to alcohol use disorders. To identify genomic factors that influence these traits, the current study (i) characterized performance of a rodent version of the BART in multiple inbred rat strains, (ii) tested the degree to which performance was under genetic control, (iii) explored sex differences in performance, and (iv) evaluated the risk-taking behavior of F1 progeny of high-risk- and low-risk-taking strains to examine modes of inheritance. METHODS: Male and female rats (N = 100) from 5 inbred strains (Wistar-Furth, Fischer-344, Lewis, Spontaneously Hypertensive, Brown Norway) and Wistar-Furth × Fischer-344 hybrids were tested in the rat-BART, as well as in tests of locomotor activity, sucrose preference, and general motivation. RESULTS: About 55% of the variance in risk-taking behavior was attributable to heritable factors. The Fischer-344 strain was the most risk-taking and the most variable in responding. The mating of low-risk-taking Wistar-Furth and Fischer-344 rats produced progeny that behaved most like the Fischer-344 strain. Consistent with prior research in this laboratory (Jentsch et al., 2010), all rats were sensitive to changes in both risk and reinforcement parameters in the rat-BART; rats decreased voluntary risk-taking in the face of increasing risk and increased lever pressing when reinforcement probabilities were reduced. CONCLUSIONS: Our results endorse a moderately heritable pattern of risk-taking behavior in rats. The behavior of the hybrid progeny suggests a polygenic model with most gene effects transmitted by mode of dominant inheritance. The identification of high-risk and low-risk strains allows for isolation of quantitative trait loci associated with task performance and for probing the relationships between risk-taking and dimensions of alcohol use disorders.

Schedule-induced polydipsia in the spontaneously hypertensive rat and its relation to impulsive behaviour.

Eight Spontaneously Hypertensive Rat (SHR), 8 Wistar-Kyoto (WKY) and 8 Wistar rats, all male, maintained at 80-85% of their free-feeding weight by controlled access to food, were exposed to a series of fixed time (FT) schedules whereby food pellets were regularly delivered regardless of the animals' behaviour. The FT values used were 9, 15, 30, 60, 120 and 180 s, with the order of presentation of the schedules among the animals being counterbalanced (except under the FT 120-s and 180-s schedules, which were successively presented as the last two of the series). Due to freely available access to water, the animals developed schedule-induced drinking under all FT schedules, marked by the characteristic bitonic function that relates the number of licks and amount of water drunk to the length of the inter-food interval. Wistar and WKY rats displayed maximum drinking under an FT 15-s schedule, with WKY rats registering lower quantities across all FT values. Among SHR rats, maximum schedule-induced polydipsia was observed under the FT 30-s schedule, with a rightward shift in the bitonic function compared to controls. For long FT values, the temporal distribution of licks within inter-food intervals was shifted slightly towards the right in the SHR rats. In a subsequent study, only the SHR and Wistar rats were used, and the animals were exposed to a delay-discounting procedure. The rats were faced with successive choices, in which they could choose between an immediate reward of one food pellet and another of four food pellets at a delay of 3, 6, 12 or 24s. In the case of the longer delays, SHR rats chose the immediate reward of lower magnitude more often than did their Wistar counterparts, and also committed a greater number of omissions during the forced-choice trials of the procedure. The results indicate that differences in schedule-induced polydipsia are related to indexes of cognitive rather than motor impulsivity, a finding in line with the theoretical idea that adjunctive behaviour is linked to operant reinforcement processes.

Intraindividual variability (IIV) in an animal model of ADHD - the Spontaneously Hypertensive Rat.

Attention-deficit/hyperactivity disorder (ADHD) is characterized by numerous behaviors including inattention, hyperactivity and impulsiveness. ADHD-affected individuals also have high intra-individual variability (IIV) in reaction time. The genetic control of IIV is not well understood. The single study of the genetics of this phenomenon in humans detected only marginal associations between genotypes at two candidate genes for ADHD and variability in response time. The Spontaneously Hypertensive Rat (SHR/NCrl) is an animal model of ADHD, expressing high activity, inattention and impulsive behavior during operant and task tests. The SHR might be useful for identifying genes for variability, but it is not known whether it also expresses high IIV, as is symptomatic of ADHD. We therefore conducted an investigation of IIV in the SHR. We used 16 SHR/NCrl rats and 15 Wistar-Kyoto (WKY/Nico) controls applying a reinforcement schedule used in the validation of the SHR as an animal model of ADHD. We represented IIV as the average absolute deviation of individual behavior within the five 18-min segments of each experimental session from the average behavioral trait value within that session ('individual phenotypic dispersion', PDi). PDi for hyperactivity, impulsiveness and inattention in the SHR and WKY rats was analyzed using nonparametric ranking by experimental session. SHR/NCrl rats had higher PDi than WKY/Nico controls for impulsiveness and inattention. There was a significant upward trend for PDi over experimental segments within sessions for attention in SHR rats, but not in WKY. PDi for hyperactivity was correlated with PDi for impulsiveness and we therefore excluded observations associated with short IRTs (< 0.67 s); dispersion in hyperactivity outside this interval was also significantly higher in SHR rats than in WKY rats. Some studies indicate the sharing of symptoms of hyperactivity and impulsiveness in SHR and ADHD-affected humans; high IIV in operant behavioral metrics suggests that the SHR may be useful in elucidating the genetic basis for IIV in humans.

Differences in home cage behavior and endocrine parametres in rats of four strains.

OBJECTIVE: The majority of studies that involve behavioral testing in different rat strains is based on measuring behavioral responses to stressful situations in a novel environment. Very little is known on the spontaneous behavior in rat strains. The aim of the present study was to compare home cage behavior and basal hormone levels in two outbred rat strains, Sprague-Dawley (SD) and Wistar as well as two inbred strains, Lewis and Spontaneously Hypertensive Rats (SHR). METHODS: Twenty-eight male rats from four strains of rats (n=7/strain) were used in this study. Behavior of each rat in his home cage was recorded by a video camera for 45 minutes during the dark phase of the day. The parameters considered included rearing, jumps, ambulation, grooming, feeding/drinking and no movements. Blood plasma was analyzed for aldosterone, plasma renin activity (PRA), adrenocorticotropin hormone (ACTH) and corticosterone by specific radioimmunoassays. RESULTS: One-way ANOVA revealed significant inter-strain differences in counts of jumps and rearing. In comparison with Sprague-Dawley and Wistar rats, Lewis rats displayed significantly more jumps and rearing. Statistical analysis showed significant inter-strain differences in the levels of aldosterone and of plasma renin activity. The highest levels of aldosterone were found in Lewis rats. Plasma renin activity was significantly lower in SHR than in Sprague-Dawley rats. Correlation analysis failed to reveal any relationships between behavioral and endocrine parameters. Significant strain differences were observed also in relative weights of the spleen, adrenals and thymus. CONCLUSION: Plasma renin activity and basal mineralocorticoid secretion did not show parallel pattern if compared among different rat strains. Locomotor activity in the home cage, which could represent general activity to be considered in evaluating emotional responses, was highest in the Lewis rats.

Aging effects on elevated plus maze behavior in spontaneously hypertensive, Wistar-Kyoto and Sprague-Dawley male and female rats.

Male and female spontaneously hypertensive (SHR), Wistar-Kyoto (WKY), and Sprague-Dawley (SD) rats were assessed at one of two ages (postnatal day 74 or 346) for open field locomotor activity and anxiety-related behavior in the elevated plus maze (EPM). In general, the SHR displayed the least anxiety-related behavior, an effect that was magnified with age. At 11 months of age, the SHR more frequently entered and remained longer in the open arms than either the SD or the WKY strains. EPM behavior of the WKY strain was much less affected by age than that of the SD strain which displayed increased anxiety-related behavior with age. At the younger age, the typical sex effects were apparent; specifically, females exhibited a shorter duration in the closed arms. While the SHR were the most active strain in the EPM at both ages, they were more active in the open field only at the older age. In general, age-related changes in open field activity mirrored those of the EPM. These results provide a more comprehensive illustration of aging-related behavioral changes in male and female SHR, WKY and SD rats.

Does hypertension alone lead to cognitive decline in spontaneously hypertensive rats?

Spontaneously hypertensive rats (SHR) represent an animal model of cognitive decline associated with hypertension. Few studies have systematically investigated this decline in aging. We assessed spatial learning performances of SHR, the genetically similar Wistar-Kyoto rats (WKY), and Sprague-Dawley rats (SD), in a water maze (WM) task. The following age ranges were studied: 6, 12, and 20 months. The results demonstrated that all three strains show the same level of impairment at the age of 20 months. The rate of cognitive decline, however, is different: both SHR and WKY show moderate degrees of impairment at all age ranges, while SD display good cognitive abilities at 6 months, declining at 12, and reaching the performance level of the other two groups at 20 months. Besides, the nine groups showed substantial differences in swim velocity and WKY exhibited a peculiar motor behavior. These results suggest the following: (a) the decline in cognitive level exhibits different trends in the three strains; (b) learning impairment of aged SHR might not be entirely explained by hypertension; (c) WKY should be used cautiously as normotensive control for SHR, due to their unusual behavior and low learning abilities; (d) analysis of escape distances is mandatory for the comparison of different strains in the WM test.

Behavioral validation of the spontaneously hypertensive rat (SHR) as an animal model of attention-deficit/hyperactivity disorder (AD/HD).

A good model of a disorder is one that: (a) mimics, although in a simpler form than the full-blown clinical case, the fundamentals of the behavioral characteristics, in this case of people with Attention-Deficit/Hyperactivity Disorder (AD/HD;face validity); (b) conforms with a theoretical rationale for the disorder (construct validity); and (c) is able to predict aspects of behavior, genetics and neurobiology previously uncharted in the clinics (predictive validity). This article discusses the Spontaneously Hypertensive Rat (SHR) and some other putative animal models of AD/HD. It is argued that although other strains and species may be hyperactive and/or show attention deficits following genetic, environmental or pharmacological interventions, the SHR is presently the only strain shown to have the major behavioral symptoms of AD/HD. This does not mean that investigating other models cannot give valuable information.

Concurrent reductions in blood pressure and metabolic rate during fasting in the unrestrained SHR.

Fasting produces multiple cardiovascular, metabolic, and behavioral responses. To examine the interrelationship between these responses, male spontaneously hypertensive rats (SHR; n = 8) implanted with cardiovascular telemetry devices were housed in metabolic chambers at 23 degrees C for 22-h daily measurements of physiological variables. The experimental apparatus was designed so that ingestive behavior was detected by photobeams and locomotion was detected by a load sensor. Cardiovascular and metabolic status were determined as both a function of the circadian cycle (12-h dark and 10-h light), as well as during periods of inactivity (no ingestion and minimal locomotion) within the dark and light phases. Data were obtained during baseline, 48-h of caloric deprivation, and 6 days of refeeding. Fasting produced significant reductions in mean arterial pressure (dark: -9.2+/-1.3 from 143.7+/-3.7 mm Hg; light: -8.6+/-1.8 from 140.1+/-3.7 mm Hg), heart rate (dark: -43.4+/-5.2 from 330.0+/-5.2 beats/min; light: -27.4+/-5.2 from 294.0+/-5.2 beats/min), and oxygen consumption (dark: -5.0+/-0.6 from 20.6+/-0.3 ml x min(-1) x kg (0.75); light: -2.7+/-0.2 from 14.9 +/-0.2 ml x min(-1) x kg(0.75)). Analysis of inactive periods during both light and dark phases revealed that these reductions were not dependent on behavioral effects. We conclude that fasting produces concurrent and interrelated reductions in cardiovascular and metabolic function in the SHR. The merging of cardiovascular telemetry, indirect calorimetry, and behavioral monitoring provides a powerful approach for investigation of the integrative physiological responses to energetic challenges.

The spontaneously hypertensive rat: insight into the pathogenesis of irritative symptoms in benign prostatic hyperplasia and young anxious males.

Recent epidemiological studies have shown that hypertensive men are more likely to undergo surgical intervention for irritative voiding symptoms from BPH than age-matched controls. Indeed, noradrenergic nerves which regulate vascular tone also participate in the functional component of bladder outlet obstruction due to BPH. Newer, less invasive therapies for BPH such as thermal therapy can relieve symptoms yet do not eliminate obstruction based on urodynamic studies. Coincidentally, drugs such as alpha-adrenoceptor antagonists, which have been thought to relieve obstruction due to a peripheral effect, can be given intrathecally in animals to relieve urinary frequency due to obstruction. Taken together these observations implicate both peripheral and central sympathetic pathways in the motor control of the urinary bladder especially with disease states. We have used the hypertensive and behaviourally hyperactive spontaneously hypertensive rat (SHR), to investigate the roles sympathetic pathways or micturition. Elevated nerve growth factor (NGF) derived from vascular and bladder smooth muscle cells of the SHR appears to direct morphological, biochemical, and functional changes. The increase in NGF can apparently be explained by stabilization of its mRNA leading to increased synthesis in NGF. Bladders from SHRs develop a profuse noradrenergic hyperinnervation compared with the control WKY strain. Since afferents supplying the SHR bladder are hypertrophied, changes in afferent pathways are also likely. These differences in innervation and NGF in the SHR may explain changes in function. SHRs void 3 times as frequently as their genetic controls. Urinary frequency can be reduced by alpha-adrenoceptor antagonists. Cystometrograms performed in SHRs reveal lower bladder capacities and micturition volumes and the presence of unstable contractions compared with the WKY rat. Intrathecal, rather than intra-arterial administration of the alpha-adrenoceptor antagonist doxazosin reduces unstable contractions in the SHR. In vitro muscle bath studies have shown enhanced responses of SHR bladder smooth muscle to alpha-adrenoceptor agonists. It is likely that upregulation of NGF production causes sensory and possibly noradrenergic pathways to elicit hyperactive voiding. Increase in NGF in the adult bladder due to pathological conditions yields similar, yet distinct, consequences for voiding behaviour and innervation. Likewise, increased NGF in adult bladders following obstruction or inflammation triggers neuronal hypertrophy, enhanced reflex activity and urinary frequency. In contrast to the SHR, hyper-innervation is not observed. Moreover, peripheral or spinal alpha-adrenoceptor blockade eliminates urinary frequency following obstruction. These observations support the role for sympathetic pathways in the motor function of the bladder, especially in congenital or adult disease states. A similar process may underlie the neuroplasticity involved in alterations after obstruction or inflammation of the lower urinary tract in humans. The SHR strain raises the possibility that a common genetic defect exists capable of predisposing to both hypertension and overactivity of the urinary bladder. Whether a genetic predisposition to sustained bladder overactivity in response to inflammatory stimuli in obstruction exists in humans is an intriguing prospect.

Strain difference in behavioral response to a new environment in rats.

Locomotor activity in rats throughout a 24-hour period in a new environment was examined for strain differences and for the capacity for adaptation to that environment. Fischer 344 rats (F344), spontaneously hypertensive rats (SHR) and Wistar normotensive Kyoto rats (WKY) were used. The horizontal locomotor activity of individual rats was measured by photocell-utilizing activity-recording devices. The locomotor activity counts on the second day, after 1 day of adaptation, were compared with those after 5 days of adaptation (on the sixth day). In WKY, there was no difference in activity at any period of the day between the second and sixth days. In SHR, the locomotor activity on the second day between 6:00 h and 9:00 h (in the light phase) and between 24:00 h and 3:00 h (in the dark phase) was higher than on the sixth day. In F344, the locomotor activity on the second day between 18:00 h and 2:00 h was higher than on the sixth day. The capacity for adaptation in SHR and F344 was thus poorer than in WKY. The poor adaptation in SHR and F344 was similar to that in depressive patients induced by moving house. These findings suggested that SHR or F344 were suitable for depression research.

Comparison of anxiety measured in the elevated plus-maze, open-field and social interaction tests between spontaneously hypertensive rats and Wistar EPM-1 rats.

On the basis of open-field and plus-maze results it has been proposed that spontaneously hypertensive (SHR) rats are less emotionally reactive than their normotensive controls, Wistar-Kyoto (WKY). However, the proposed "anxiolytic characteristics" of SHR rats may be questioned in view of the significant hypoactivity presented by WKY rats. In the present study, the behavioral response of spontaneously hypertensive (SHR) and equally active normotensive Wistar EPM-1 (EPM-1) rats (4-month old males, 10-13 animals per group) were evaluated in the open-field, social interaction and elevated plus-maze tests. In the open-field study, no differences were observed for total locomotion frequency and immobility duration, but SHR rats presented a higher central square locomotion frequency (23.8 +/- 2.1 vs 10.3 +/- 1.6) as compared to EPM-1. SHR rats also exhibited a greater duration of social interaction when compared to EPM-1 rats (mean +/- SEM values were 113.9 +/- 8.7 s for SHR vs 72.7 +/- 8.6 s for EPM-1 rats after 8-min observation). In the elevated plus-maze test, SHR rats presented an increased percent of entries (52.8 +/- 3.3 vs 28.3 +/- 4.5) and time in the open arms (65.6 +/- 6.0 vs 11.1 +/- 1.9) as compared to EPM-1 rats, although the total number of arm entries (9.2 +/- 0.9 vs 9.7 +/- 1.0) was unchanged. These results suggest that the "anxiolytic behavior" of SHR rats in relation to normotensive controls is not related to differences in motility levels.

Comparison of anxiety measured in the elevated plus-maze, open-field and social interaction tests between spontaneously hypertensive rats and Wistar EPM-1 rats

On the basis of open-field and plus-maze results it has been proposed that spontaneously hypertensive (SHR) rats are less emotionally reactive than their normotensive controls, Wistar-Kyoto (WKY). However, the proposed anxiolytic characteristics of SHR rats may be questioned in view of the significant hypoactivity presented by WKY rats. In the present study, the behavioral response of spontaneously hypertensive (SHR) and equally active normotensive Wistar EPM-1 (EPM-1) rats (4-month old males, 10-13 animals per group) were evaluated in the open-field, social interaction and elevated plus-maze tests. In the open-field study, no differences were observed for total locomotion frequency and immobility duration, but SHR rats presented a higher central square locomotion frequency (23.8 +/- 2.1 vs 10.3 +/- 1.6) as compared to EPM-1. SHR rats also exhibited a greater duration of social interaction when compared to EPM-1 rats (mean +/- SEM values were 113.9 +/- 8.7 s for SHR vs 72.7 +/- 8.6 s for EPM-1 rats after 8-min observation). In the elevated plus-maze test, SHR rats presented an increased percent of entries (52.8 +/- 3.3 vs 28.3 +/- 4.5) and time in the open arms (65.6 +/- 6.0 vs 11.1 +/- 1.9) as compared to EPM-1 rats, although the total number of arm entries (9.2 +/- 0.9 vs 9.7 +/- 1.0) was unchanged. These results suggest that the anxiolytic behavior of SHR rats in relation to normotensive controls is not related to differences in motility levels

The spontaneously hypertensive rat (SHR) as an animal model of childhood hyperactivity (ADHD): changed reactivity to reinforcers and to psychomotor stimulants.

Childhood hyperactivity (attention-deficit hyperactivity disorder, ADHD) is a behavior disorder affecting 2-6% of grade-school children. The main symptoms are attention problems and hyperkinesis. The disorder is commonly treated with psychomotor stimulants, usually methylphenidate hydrochloride (ritalin) or d-amphetamine. Neither the cause of the disorder nor the basis of the effectiveness of the drug treatment is well understood. Differences in reinforcement processes have been implicated as part of the underlying problem. The main purpose of the present research was to investigate reinforcement processes and motor characteristics with and without stimulant medication in SHR, as an animal model of ADHD, and WKY controls, its normoactive progenitor strain. SHR behavior turned out to be more sensitive to immediate reinforcement and proportionately less sensitive to delayed reinforcement when compared to the behavior of WKY, as demonstrated by systematic changes in rates of responding throughout fixed-interval schedules of reinforcement of bar-presses by water. The psychomotor stimulants weakened the control by immediate reinforcers and strengthened the control by delayed reinforcers, with the effect of the drugs being more pronounced in WKY than in SHR. The results are consistent with clinical observations that ADHD children are less willing than others to accept "delayed gratification" and that methylphenidate increases the control of delayed reward over their behavior.