reparto di neuroscienze comportamentali, dip. biologia ... benessere animale/approcci... · reparto...
TRANSCRIPT
Reparto di Neuroscienze comportamentali,
Dip. Biologia cellulare e Neuroscienze
Istituto Superiore di Sanità, Roma
Animal Welfare
Does the mouse have what it wants?
Is the mouse healthy?
Factors affecting phenotype
Genes… … and environment
Standardization
Standardization: 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
Ethical question:● Implications for the animals?
animal welfare
Scientific question:● Implications for the research?
scientific validity
Effects of the environment on animal phenotype: Two questions.
Stereotypic behaviour
Cage-induced abnormal behaviours: Stereotypies
Stereotypies
DefinitionRepetitive, invariantbehavioural pattern withoutobvious goal or function
CausationFrustration of essential behavioural needs
Consequences?
Polar Bear at Zürich ZooFoto: H. Hediger
StereotipieComportamenti relativamente invariati e ripetitivi, apparentemente privi di funzione nel contesto in cui vengono espressi (Mason, 1991)
“Le stereotipie possono rappresentare un chiaro sintomo di stress e una strategia di “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 of essential behavioural needs
• Stereotypies reflect the disruption of neural mechanisms involved in the inhibitory control of behaviour
• Stereotypies are pathological consequences of inappropriate housing conditions
• Current standard housing conditions for laboratory mice seem inappropriate
Stereotypies in humans:
Symptom for psychiatric disorderse.g. schizophrenia, autism
Symptom for lesions and disorders of specific brain regions (basal ganglia)
Stereotypic behaviour
A d u lt s
P e r ia d o le s c e n t s
S A L I N EA
ctiv
ity
rate
*
3 0 6 0 9 0 1 2 00
1
2
3
4 A M P H 1 0
M in u t e s
*
* *
0
1
2
3
4
0
1
2
3
4 A M P H 2
* * * *
3 0 6 0 9 0 1 2 0
M in u t e s3 0 6 0 9 0 1 2 0
M in u t e s
1 0 0
5 0 0
1 0 0 0
1 5 0 0
2 0 0 0
S A L I N E
CO
RT
(% o
f bas
elin
e)
1 5 3 0 1 2 0 1 5 3 0 1 2 0
A M P H 1 0A M P H 2
1 5 3 0 1 2 0
M in u t e sM in u t e sM in u t e s
M in u t e s
5 1 5 3 0 6 0 9 0 1 2 00
5 0
1 0 0
1 5 0
2 0 0
**
**
Mea
n du
rati
on (
s) o
f
each
ste
reot
ypy
epis
ode
A M P H 1 0
RELAZIONE TRA LIVELLI DI PLASMATICI DI CORTICOSTERONE E ESPRESSIONE DI STEREOTIPIE COMPORTAMENTALI in risposta a iniezione di anfetamina (10 mg/kg)
STUDYThe experience of stressful events in early life can turn to an increased predisposition to mood disorders at adulthood. Several data indicate in prenatally stressed rats increased anxiety and emotionality.
The capacity of a precocious environmental intervention to normalize the behavioural and immunological dysfunctions produced by a stressed pregnancy was investigated. In order to assess new therapeutic strategies, an environmental enrichment approach was used.
Pregnant rats underwent three-45 min/day sessions of prenatal restraint stress (PS) on gestation days 11 to 21, and offspring were assigned to either enriched-environment or standard living cages throughout adolescence (pnd 22-43).
Weaning
STRESS
P 21
Pregnancy Birth Adolescence
P 65E 10E 0
Non-enriched environmentEnriched environment
(2 rats per cage)
Prenatal Stress and depression: Therapeutic approach by means of environmental stimulation
Nel nostro modello (ratti sottoposti a stress prenatale, in rosso), la possibilità di interagire durante l’adolescenza con un ambiente arricchito (in verde) ha prodotto una significativa normalizzazione della risposta neuro-endocrina a uno stress acuto (vedi figura) e del repertorio comportamentale (stati d’ansia, interazioni sociali).
Ambiente arricchito
)
0
5
10
15
20
25
Cor
ticos
tero
ne(µ
g/m
l)
0 20 60 Time (min)
*
$
$
ACUTE STRESS
PS-EC-NE
C-E
PS-NE
Gabbia standard
Environmental enrichment and social play behaviour
Environmental enrichment reverses the reduction of play behaviour induced by Prenatal Stress
0
20
40
60
80
100
120
140
Freq
uenc
y of r
ough
-and
- tum
ble p
lay
Controls PS Controls PS
Non - Enriched Enriched
*
##
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 *
-COND **
-GROUP x COND **
-DRUG ns
-COND **
-DRUG **
-COND x DRUG **
STATISTICAL RESULTS :
- COND *
- DRUG *
- GROUP x COND *
- COND x DRUG **
- for hypothalamus: COND*
VI RINGRAZIAMO PER L’ATTENZIONE