Reparto Di Neuroscienze Comportamentali, Dip. Biologia .

Reparto di Neuroscienze comportamentali,Dip. Biologia cellulare e NeuroscienzeIstituto Superiore di Sanità, Roma

Animal WelfareDoes the mouse have what itwants?Is the mouse healthy?

Factors affecting phenotypeGenes and environment

StandardizationStandardization: Aims minimize individual differences within study populations(within-experiment variation)maximize test sensitivity (reduction of sample size!) minimize differences between study populations(between-experiment variation)maximize reproducibility of results

Effects of the environment on animal phenotype: Two questions.Ethical question: Implications for the animals?animal welfareScientific question: Implications for the research?scientific validity

Stereotypic behaviourCage-induced abnormal behaviours: Stereotypies

StereotypiesDefinitionRepetitive, invariantbehavioural pattern withoutobvious goal or functionCausationFrustration of essential behaviouralneedsConsequences?Polar Bear at Zürich ZooFoto: H. Hediger

etitivi,apparentemente privi di funzione nel contesto in cui vengonoespressi (Mason, didiunstresspossonochiaroeuna“adattamento”allo stimolo stressante ”Lawrence A.B. and Rushen J. 1993. Stereotypic animal behaviour: Fundamentals andapplications to welfare. CAB International, pp. 212

Stereotypic behaviour Stereotypies develop from behavioural responses to the frustration ofessential behavioural needs Stereotypies reflect the disruption of neural mechanisms involved in theinhibitory control of behaviour Stereotypies are pathological consequences of inappropriate housingconditions Current standard housing conditions for laboratory mice seem inappropriate

Stereotypic behaviourStereotypies in humans:Symptom for psychiatric disorderse.g. schizophrenia, autismSymptom for lesions and disorders of specificbrain regions (basal ganglia)

A ct iv it y rat eRELAZIONE TRA LIVELLI DI PLASMATICI DI CORTICOSTERONE EESPRESSIONE DI STEREOTIPIE COMPORTAMENTALIinS diA LanfetaminaIN EAM PH 2risposta a iniezione(10 mg/kg)AM P H 1 0444333222** ** ** *111*003 06 09 01 2 03 09 001 2 03 06 0M in u t e sM in u t e sSALIN E9 01 2 0M in u t e sAM PH 2AM PH 1 02 0 0 01 5 0 01 0 0 05 0 01 0 03 0M in u t e s1 2 01 53 01 2 01 53 0M in u t e sAM PH 1 02 0 0P e r ia d o le s c e n t sA d u lt s1 2 0M in u t e seac h s t e re ot y py e pis od e1 5Me an durat io n (s ) o fCOR T (% of bas e line)6 01 5 01 0 0**5 0**051 53 06 0M in u t e s9 01 2 0

STUDYThe experience of stressful events in early life can turn to an increasedpredisposition to mood disorders at adulthood. Several data indicate inprenatally stressed rats increased anxiety and emotionality.The capacity of a precocious environmental intervention to normalize thebehavioural and immunological dysfunctions produced by a stressed pregnancywas investigated. In order to assess new therapeutic strategies, anenvironmental enrichment approach was used.Pregnant rats underwent three-45 min/day sessions of prenatal restraintstress (PS) on gestation days 11 to 21, and offspring were assigned toeither enriched-environment or standard living cages throughout adolescence(pnd 22-43).

Prenatal Stress and depression: Therapeutic approach by means of environmental stimulationSTRESSE0E 10PregnancyP 21BirthNon-enriched environment(2 rats per cage)WeaningP 65AdolescenceEnriched environment

Ambiente arricchitoGabbia standardCorticosterone (µg/ml)25 ) 20PS-NE15*PS-EC-NE10C-E50ACUTESTRESS020Time (min)60Nel nostro modello (ratti sottoposti a stressprenatale, in rosso), la possibilità di interagiredurante l’adolescenza con un ambiente arricchito (inverde)haprodottounasignificativanormalizzazione della risposta neuro-endocrina auno stress acuto (vedi figura) e del repertoriocomportamentale (stati d’ansia, interazioni sociali).

Environmental enrichment and social play behaviourFrequency of rough-and- tumble play140120100##80*6040200ControlsPSNon - EnrichedControls PSEnrichedEnvironmental enrichment reverses the reduction of play behaviourinduced by Prenatal Stress

STATISTICAL RESULTS:-GROUP **- GROUP x COND *- DRUG *- GROUP x DRUG *- COND x DRUG*

STATISTICAL RESULTS :- GROUP x COND *- DRUG*- GROUP x DRUG **- COND x DRUG**

-GROUP *- GROUP x COND *-COND- COND x DRUG****-GROUP x COND **-DRUGns- for hypothalamus: COND*-COND**-DRUG**STATISTICALRESULTS :-COND x DRUG **- COND *- DRUG *

VI RINGRAZIAMO PER L’ATTENZIONE

Reparto di Neuroscienze comportamentali, Dip. Biologia cellulare e Neuroscienze Istituto Superiore di Sanità, Roma. Animal Welfare Does the mouse have what it