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Gaburro, Stefano (2009) Autonomic function in mice with altered anxiety/depression related behavior. [Tesi di dottorato]

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Abstract (inglese)

Autonomic dysregulation has been described in patients suffering from anxiety and depression disorders. The vast majority of animal studies investigating autonomic function in anxiety and depression involve “non pathological” models. Thus, the aim of the present study was to investigate parameters of autonomic regulation (e.g. body temperature, heart rate and heart rate variability) in a mouse model selectively bred for high innate anxiety (HAB) versus normal anxiety like behaving mice (NAB).
Basal (home cage) and mild unconditioned stressor conditions (e.g. novel cage, open field) did not reveal any difference in heart rate or body temperature between HAB and NAB mice. Surprisingly, when we investigated heart rate variability during conditioned stressors (e.g. fear conditioning), we revealed reduced heart rate variability (HRV) associated with impaired fear extinction in HAB versus NAB mice. This finding of reduced HRV suggests a strong resemblance to what is observed in patients suffering from anxiety and depressive disorders. Moreover, the enhanced anxiety- and depression-related behavior was attenuated after successful chronic NK1 receptor antagonist treatment in HAB mice. The behavioral effect of the NK1 receptor antagonist was associated with normalization of the reduced HRV. These findings demonstrate that heart rate variability is a useful additional diagnostic marker, sensitive to successful drug treatment, characterizing high anxiety and depression trait. Thus, futures studies will elucidate if on the basis of HRV it will be possible to predict successful drug treatment in high anxiety and depression patients.

Abstract (italiano)

Disturbi psico-affettivi, come sintomatologie ansioso-depressive, sono state spesso associate con alterazioni del sistema cardiovascolare, che a lungo andare può dare luogo all´insorgenza di malattie cardiovascolari croniche e quindi ad un incremento del rischio di associata morbilità e mortalità. Purtroppo, la maggior parte degli studi animali che analizzano la stretta incidenza tra disturbi psico-affettivi e il sistema cardiovascolare, utilizzano modelli animali cosiddetti non patologici. Di conseguenza, tali studi mancano di informazioni sulle strette analogie che intercorrono nella regolazione neuro-vascolare in uno stato patologico come ansia e depressione. Quindi oggetto della presente tesi è l´analisi di parametri cardiovascolari (temperature corporea, frequenza cardiaca e variabilità della frequenza cardiaca) in un modello animale selezionato per innato comportamento ansioso-depresso HAB (molto ansioso) e normal ansioso (NAB), quindi mimando la vasta eterogeneità presente negli studi clinici in disturbi psico-affettivi.
In condizioni basali e in una serie di test comportamentali considerati mediamente stressanti (novel cage, open field), non sono state rilevate differenze nella frequenza cardiaca e nella temperatura corporea tra le due linee di topo. Quando invece è stata studiata la variabilità della frequenza cardiaca (HRV), in un test comportamentale in cui viene misurata la paura dei topi (fear conditioning), associata ad un’esagerata espressione della paura nella linea di topi HAB è stata trovata una ridotta HRV. Questo riflette quanto osservato in pazienti con sintomatologia ansioso-depressiva in cui una ridotta HRV è correlata ad un’aumentata espressione della paura.
Poi, con l´ausilio di un antidepressivo sperimentale ancora in fase di sviluppo, appartenente alla famiglia degli antagonisti del recettore NK1, si è riusciti a normalizzare HRV con coincidente riduzione del comportamento molto ansioso e depresso nella linea di topi HAB. Questi risultati dimostrano che HRV può essere utilizzata come marker per caratterizzare individui con alti livelli di ansia e depressione. Inoltre, studi futuri chiariranno se sulla base di HRV sia possibile identificare effetti positivi di un trattamento farmacologico per ansia e depressione ancor prima di osservare gli effetti comportamentali.

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Tipo di EPrint:Tesi di dottorato
Relatore:Giusti, Pietro
Correlatore:Striessnig, Jörg
Dottorato (corsi e scuole):Ciclo 21 > Corsi per il 21simo ciclo > FARMACOLOGIA MOLECOLARE E CELLULARE
Data di deposito della tesi:30 Gennaio 2009
Anno di Pubblicazione:2009
Parole chiave (italiano / inglese):autonomic system, HRV, anxiety,depression, behavior, HAB mice, NAB mice
Settori scientifico-disciplinari MIUR:Area 05 - Scienze biologiche > BIO/14 Farmacologia
Struttura di riferimento:Dipartimenti > Dipartimento di Farmacologia ed Anestesiologia "E. Meneghetti"
Codice ID:1779
Depositato il:30 Gen 2009
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