Role of Serotonin in a Genetic Murine Model of Psychiatric Vulnerability
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Transcript of Role of Serotonin in a Genetic Murine Model of Psychiatric Vulnerability
Role of Serotonin in a Genetic Murine Model of Psychiatric Vulnerability
Università degli Studi di Roma La SapienzaFacoltà di Medicina e di Psicologia
Neuroscienze Cognitive e Riabilitazione Psicologica
Tesi di Laurea Magistrale
Supervisor: Prof.ssa Cristina Orsini
Co-advisor: Prof.ssa Simona CabibLaureando: Gianvito Lagravinese
Anno Accademico 2015/2016
Obey impulsive action and choice Premature responses Inhability to hold or stop an action Lack of planning Extreme reactivity to reward associated stimuli
Impulsivity
Substance abuse Psychiatric disorders:
APD Bipolar Disorder
(maniacal) Borderline disorder
“Disinhibition” dimension trait (DSM V )
Disihinibitory control
Impulsivity & SerotoninSerotonin (5-HT) exerts an inhibitory control on impulsive behaviour
Clinical studies Preclinical studies
Depletions ↑ impulsivity
SSRI drugs ↓ premature responses ↓ cue reactivity to drugs
associated stimuli (conditionated craving)
Pavlovian Approach (autoshaping) Ripeated
presentation lever-food
Individual variability in the developing of conditionate behaviour
Sign-Tracking
Sign- Tracker highly sensivity to reward associated stimuli
Sign-tracker Fenotype Predictive of impulsivity
Genotipic serotonergic differences DBA mice allelic variance of gene TPH2:
↓ functionality of 5-HT (compared to c57) ↓ basal firing of 5-HT in mPFC
Sign-Tracking e Serotonin
5-HT Depletion to C57 mice (Campus, 2016) allows Sign-Tracking behaviour expression
C57
not impulsive & neither Sign-tracker
DBA
impulsive & Sign-Tracker
Autoshaping Training: 35 trial / session, 11 days Treatment: 30 min before session (day 12)
Acute administration of fluoxetine (SSRI) 10 mg/kg (i.p.)
Experimental Design
Behavioural Index: Lever Approach Magazine Approach PCA Index: indicates the behaviour prevalence
Pavlovian Conditioned Approach (PCA)
Fluoxetine reduced magazine entry but did not alter the food intake
Conclusions Enhancing serotonin could have increased
patience by improving the ability of waiting the reward
Limitations: Acute administration could have not be enough
to enhance 5-HT levels Systemic administration does not allow to
understand the specific action of 5-HT 5-HT could be necessary to inhibit the
development of sign-tracking but not to inhibits its expression