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

Serotonin enhancement in DBA strain suppress the sign-tracking behaviour

Hypothesis

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

Lever Approach

Magazine Approach

Pavlovian Conditioned Approach (PCA)

Fluoxetine reduced magazine entry but did not alter the food intake

Trial %

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

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