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A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment.

Gaburro S, Stiedl O, Giusti P, Sartori SB, Landgraf R, Singewald N - Int. J. Neuropsychopharmacol. (2011)

Bottom Line: Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety.Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results.These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.

ABSTRACT
Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

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High anxiety behaviour (HAB) and normal anxiety-like behaviour (NAB) mice displayed similar basal and stress-induced locomotor activity and heart rate (HR) patterns upon novel cage exposure. Compared to baseline values, exposure to a novel environment in both lines caused an increase in (a) locomotor activity and (b) HR [expressed as beats per min (bpm)]; whereas (c) HR variability (root mean square of successive RR interval differences; RMSSD) was reduced. Locomotor activity and autonomic responses did not differ between HAB (□) and NAB mice (▪) under both basal and novelty conditions. Data are means±s.e.m. (n=8/line). ### p<0.001 novelty vs. baseline.
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fig002: High anxiety behaviour (HAB) and normal anxiety-like behaviour (NAB) mice displayed similar basal and stress-induced locomotor activity and heart rate (HR) patterns upon novel cage exposure. Compared to baseline values, exposure to a novel environment in both lines caused an increase in (a) locomotor activity and (b) HR [expressed as beats per min (bpm)]; whereas (c) HR variability (root mean square of successive RR interval differences; RMSSD) was reduced. Locomotor activity and autonomic responses did not differ between HAB (□) and NAB mice (▪) under both basal and novelty conditions. Data are means±s.e.m. (n=8/line). ### p<0.001 novelty vs. baseline.

Mentions: Novelty exposure was used to determine the effects of an unconditioned challenge on locomotor activity and autonomic parameters in HAB and NAB mice. There was no line×novelty interaction for locomotor activity (F1,60=3.57, p>0.05; Fig. 2 a), HR (F1,60=0.21, p>0.05; Fig. 2 b) or HR variability (F1,60=1.25, p>0.05; Fig. 2 c). ANOVA yielded a significant novelty effect for locomotor activity (F1,60=566.99, p<0.001; Fig. 2 a) indicating a significant increase in locomotor activity in both lines during novelty exposure compared to baseline values. A significant novelty effect was also found for HR (F1,60=692.38, p<0.001, Fig. 2 b) and HR variability (F1,60=168.28, p<0.001; Fig. 2 c). While HR levels were increased by novelty in both lines compared to baseline values, HR variability was reduced.


A mouse model of high trait anxiety shows reduced heart rate variability that can be reversed by anxiolytic drug treatment.

Gaburro S, Stiedl O, Giusti P, Sartori SB, Landgraf R, Singewald N - Int. J. Neuropsychopharmacol. (2011)

High anxiety behaviour (HAB) and normal anxiety-like behaviour (NAB) mice displayed similar basal and stress-induced locomotor activity and heart rate (HR) patterns upon novel cage exposure. Compared to baseline values, exposure to a novel environment in both lines caused an increase in (a) locomotor activity and (b) HR [expressed as beats per min (bpm)]; whereas (c) HR variability (root mean square of successive RR interval differences; RMSSD) was reduced. Locomotor activity and autonomic responses did not differ between HAB (□) and NAB mice (▪) under both basal and novelty conditions. Data are means±s.e.m. (n=8/line). ### p<0.001 novelty vs. baseline.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3198175&req=5

fig002: High anxiety behaviour (HAB) and normal anxiety-like behaviour (NAB) mice displayed similar basal and stress-induced locomotor activity and heart rate (HR) patterns upon novel cage exposure. Compared to baseline values, exposure to a novel environment in both lines caused an increase in (a) locomotor activity and (b) HR [expressed as beats per min (bpm)]; whereas (c) HR variability (root mean square of successive RR interval differences; RMSSD) was reduced. Locomotor activity and autonomic responses did not differ between HAB (□) and NAB mice (▪) under both basal and novelty conditions. Data are means±s.e.m. (n=8/line). ### p<0.001 novelty vs. baseline.
Mentions: Novelty exposure was used to determine the effects of an unconditioned challenge on locomotor activity and autonomic parameters in HAB and NAB mice. There was no line×novelty interaction for locomotor activity (F1,60=3.57, p>0.05; Fig. 2 a), HR (F1,60=0.21, p>0.05; Fig. 2 b) or HR variability (F1,60=1.25, p>0.05; Fig. 2 c). ANOVA yielded a significant novelty effect for locomotor activity (F1,60=566.99, p<0.001; Fig. 2 a) indicating a significant increase in locomotor activity in both lines during novelty exposure compared to baseline values. A significant novelty effect was also found for HR (F1,60=692.38, p<0.001, Fig. 2 b) and HR variability (F1,60=168.28, p<0.001; Fig. 2 c). While HR levels were increased by novelty in both lines compared to baseline values, HR variability was reduced.

Bottom Line: Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety.Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results.These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Toxicology, Institute of Pharmacy and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Austria.

ABSTRACT
Increasing evidence suggests that specific physiological measures may serve as biomarkers for successful treatment to alleviate symptoms of pathological anxiety. Studies of autonomic function investigating parameters such as heart rate (HR), HR variability and blood pressure (BP) indicated that HR variability is consistently reduced in anxious patients, whereas HR and BP data show inconsistent results. Therefore, HR and HR variability were measured under various emotionally challenging conditions in a mouse model of high innate anxiety (high anxiety behaviour; HAB) vs. control normal anxiety-like behaviour (NAB) mice. Baseline HR, HR variability and activity did not differ between mouse lines. However, after cued Pavlovian fear conditioning, both elevated tachycardia and increased fear responses were observed in HAB mice compared to NAB mice upon re-exposure to the conditioning stimulus serving as the emotional stressor. When retention of conditioned fear was tested in the home cage, HAB mice again displayed higher fear responses than NAB mice, while the HR responses were similar. Conversely, in both experimental settings HAB mice consistently exhibited reduced HR variability. Repeated administration of the anxiolytic NK1 receptor antagonist L-822429 lowered the conditioned fear response and shifted HR dynamics in HAB mice to a more regular pattern, similar to that in NAB mice. Additional receiver-operating characteristic (ROC) analysis demonstrated the high specificity and sensitivity of HR variability to distinguish between normal and high anxiety trait. These findings indicate that assessment of autonomic response in addition to freezing might be a useful indicator of the efficacy of novel anxiolytic treatments.

Show MeSH
Related in: MedlinePlus