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

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

Physiology & Behavior

Volume 52, Issue 1, July 1992, Pages 49-57

https://doi.org/10.1016/0031-9384(92)90432-2 Get rights and content

Abstract

The spontaneously hypertensive rat (SHR) is behaviorally hyperactive relative to the Wistar-Kyoto rat (WKY). By breeding SHR with WKY, followed by inbreeding, two new strains have been developed in which hypertension seems to be separated from hyperactivity to novel stimuli: the WKHT and the WKHA strains. The main purpose of the present study was to determine which behavioral characteristics of SHR have been dissociated from the hypertensive trait in the WKHA strain. Male SHR, WKY, WKHT, and WKHA were subjected to three protocols: 1) Two forced-exploration tests, where the results showed that both the SHR and the WKHA rats were hyperactive. 2) A free-exploration open field, where the SHR was more active than the other strains, showing shorter latencies to leave the home cage, spending more time in the field, ambulating and rearing more. Furthermore, the WKHT behavior was more similar to the SHR behavior than the WKHA behavior. 3) A two-component schedule of reinforcement, where one component (fixed-interval 2 min) was signaled by houselight on and the other (extinction, EXT) by houselight off. In this test, the SHR behavior was markedly different from that of the three other strains: the fixed-interval scallop, the accelerated responding towards the end of the interval, was steeper in SHR than in the other groups. The SHR emitted more responses during the extinction component of the schedule. The SHR hyperactivity was dependent upon the reinforcement value of the water deliveries and was increased even further by sensory-reinforcing response feedback lights. Thus, the hyperactivity of the WKHA strain seems to be less pervasive than that of the SHR. It is concluded that both SHR and WKHA show increased reactivity to stimuli: SHR to stimuli acting as reinforcers and WKHA to novel, aversive stimuli.

References (28)

E.D. Hendley et al.
Sympathetic-adrenal medullary response to stress in hyperactive and hypertensive rats
Physiol. Behav.
(1988)
E.D. Hendley et al.
Age, strain and sex differences in activity and habituation in SHR and WKY rats
Physiol. Behav.
(1985)
E.D. Hendley et al.
Inbreeding of Wistar-Kyoto rat strain with hyperactivity but without hypertension
Behav. Neural Biol.
(1986)
S. Knardahl
Behavioral responsiveness and habituation to discrete auditory and olfactory stimuli in spontaneously hypertensive, two-kidney one-clip hypertensive, and normotensive rats
Behav. Neural Biol.
(1982)
S. Knardahl et al.
Passive-avoidance behavior of spontaneously hypertensive rats
Behav. Neural Biol.
(1984)
S. Knardahl et al.
Open-field behavior of spontaneously hypertensive rats
Behav. Neural Biol.
(1979)
S. Knardahl et al.
Two-way active avoidance behavior of spontaneously hypertensive rats: Effect of intensity of discontinuous shock
Behav. Neural Biol.
(1982)
R. McCarty
Stress, behavior and experimental hypertension
Neurosci. Biobehav. Rev.
(1983)
D.C. Tucker et al.
Behavioral correlates of spontaneous hypertension
Neurosci. Biobehav. Rev.
(1981)
B. Wultz et al.
The spontaneously hypertensive rat as an animal model of attention-deficit hyperactivity disorder: Effects of methylphenidate on exploratory behavior
Behav. Neural Biol.
(1990)

R.J. Blanchard et al.

Defensive reactions and exploratory behavior in rats

J. Comp. Physiol. Psychol.

(1974)

A.C. Catania

Learning

(1984)

A.C. Catania et al.

Reinforcement schedules: Retroactive and proactive effects of reinforcers inserted into fixed-interval performance

J. Exp. Anal. Behav.

(1988)

B.P. Dews

The effects of multiple S periods on responding on a fixed-interval schedule

J. Exp. Anal. Behav.

(1962)

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Individual differences in reward-related learning are relevant to many behavioral disorders. Sensory cues that predict reward can become incentive stimuli that adaptively support behavior, or alternatively, cause maladaptive behaviors. The spontaneously hypertensive rat (SHR) expresses a genetically determined elevated sensitivity to delay of reward, and has been extensively studied as a behavioral model for attention deficit hyperactivity disorder (ADHD). We investigated reward-related learning in the SHR, comparing them to Sprague-Dawley (SD) rats as a reference strain. A standard Pavlovian conditioned approach task was used, in which a lever cue was followed by reward. Lever presses could occur while the lever was extended, but had no effect on reward delivery. The behavior of both the SHRs and the SD rats showed that they learnt that the lever cue predicted reward. However, the pattern of behavior differed between the strains. During lever cue presentation, SD rats pressed the lever more often and made fewer magazine entries than SHRs. When lever contacts that did not result in lever presses were analyzed, there was no significant difference between SHRs and SDs. These results suggest that the SHRs attributed less incentive value to the conditioned stimulus than the SD rats. During the presentation of the conditioned cue, cue directed responses are called sign tracking responses, whereas responses directed towards the food magazine are called goal tracking responses. Analysis of behavior using a standard Pavlovian conditioned approach index to quantify sign and goal tracking tendencies showed that both strains had a tendency towards goal tracking in this task. However, the SHRs showed a significantly greater goal tracking tendency than the SD rats. Taken together, these findings suggest that attribution of incentive value to reward predicting cues is attenuated in SHRs, which might explain their elevated sensitivity to delay of reward.
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Attention deficit hyperactivity disorder (ADHD) is a polygenic neurodevelopmental disorder that affects 8–12 % of children and >4 % of adults. Environmental factors are believed to interact with genetic predispositions to increase susceptibility to ADHD. No existing rodent model captures all aspects of ADHD, but several show promise. The main genetic models are the spontaneous hypertensive rat, dopamine transporter knock-out (KO) mice, dopamine receptor subtype KO mice, Snap-25 KO mice, guanylyl cyclase-c KO mice, and latrophilin-3 KO mice and rats. Environmental factors thought to contribute to ADHD include ethanol, nicotine, PCBs, lead (Pb), ionizing irradiation, 6-hydroxydopamine, neonatal hypoxia, some pesticides, and organic pollutants. Model validation criteria are outlined, and current genetic models evaluated against these criteria. Future research should explore induced multiple gene KOs given that ADHD is polygenic and epigenetic contributions. Furthermore, genetic models should be combined with environmental agents to test for interactions.
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The relationship between hypertension and sleep-related movement disorders has been hypothesized for humans, but the causes and mechanisms have not been elucidated. We investigated whether an alteration in blood pressure (BP) induced by physical exercise and/or an angiotensin-converting enzyme inhibitor (enalapril) could affect locomotor activity in spontaneously hypertensive rats, with emphasis on the dopaminergic system. We used SHR and normotensive Wistar rats distributed into 4 groups for each strain: control, physical exercise, enalapril and physical exercise + enalapril. Physical exercise was performed on a treadmill, and enalapril was administered by gavage, both for 8 weeks. During this period, locomotor activity was evaluated in an open field test, and BP was evaluated by tail plethysmography. Dopaminergic receptors, dopamine transporter and tyrosine hydroxylase levels at the striatum were evaluated by Western blotting. The control group of spontaneously hypertensive rats showed higher BP, increased activity in the open field test and lower levels of D2 receptors and tyrosine hydroxylase compared with all other groups throughout the experimental period. In general, physical exercise and enalapril attenuated these alterations. This study suggested the existence of comorbidity between hypertension and sleep-related movement disorders in spontaneously hypertensive rats. Physical exercise and enalapril conferred protection for both hypertension and the observed behavioral changes. In addition, these treatments led to changes in dopaminergic signaling in the striatal region (i.e., D2 receptor, TH and DAT).
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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.
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ArticleBehavior of hypertensive and hyperactive rat strains: Hyperactivity is not unitarily determined

Abstract

Physiol. Behav.

Physiol. Behav.

Behav. Neural Biol.

Behav. Neural Biol.

Behav. Neural Biol.

Behav. Neural Biol.

Behav. Neural Biol.

Neurosci. Biobehav. Rev.

Neurosci. Biobehav. Rev.

Behav. Neural Biol.

Defensive reactions and exploratory behavior in rats

J. Comp. Physiol. Psychol.

Learning

Reinforcement schedules: Retroactive and proactive effects of reinforcers inserted into fixed-interval performance

J. Exp. Anal. Behav.

The effects of multiple S periods on responding on a fixed-interval schedule

J. Exp. Anal. Behav.

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