Impulsivity, risk proneness, and poor decision-making are common behavioural symptoms observed in impulse-control disorders, a neuropsychiatric category including attention-deficit/hyperactivity disorder (ADHD) as well as pathological gambling (PG). ADHD, affecting about 3-5% of children, is characterized by traits of inattention, impulsivity, and motor hyperactivity. PG, affecting 0.2-5.3% of adults and 3.5-8.0% of adolescents, is highly comorbid with a range of addictive disorders and is frequently observed in ADHD adolescents and adults. Interest is rising for animal modelling of impaired behavioural inhibition: in order to test the lack of self-control abilities and/or impulsive decision-making, many operant paradigms have been developed, involving a choice with delayed and/or uncertain reinforcers. These choice-based operant tasks, which assess the balance between motivational drives and inhibitory self-control, are extremely useful for investigating reward-discounting processes and their modulation by 5-HT-targeting manipulations. The present thesis is thus focused on the modelling, in laboratory rats, of key symptoms like impulsivity and gambling proneness. Specifically, the first part (chapters 2 and 3) includes a methodological refinement of the operant tasks used, such as Intolerance-to-Delay (ID) and Probabilistic-Delivery (PD) tasks, whereas the second part (chapters 4 and 5) relates to experimental manipulations of the serotonergic influence on these symptoms”. In chapter 2, we report about the marked impact exerted by duration of post-reward timeout (TO) and daily session length (SL) on impulsive choice and gambling proneness in the ID and PD tasks respectively. In chapter 3, we discuss about the role of different methodological improvements in the PD task, implemented (on both the paradigm and the apparatus) to allow testing of adolescent rats in the home-cage, while socially living and within the limited span of this developmental phase. In the fourth chapter, serotonin (5-HT) levels have been manipulated by means of a diet deficient in its precursor, tryptophan (TRP); in the fifth chapter, serotonin transporter (SERT) levels within the hippocampus of rats have been altered through genetic engineering techniques that allow to modulate in-vivo gene expression in specific brain areas. The findings reported in chapter 4 show that TRP depletion leads to changes in behavioural responses related to decision-making as well as a gambling proneness. In chapter 5, we demonstrated that a partial silencing of the SERT-encoding gene is effective in inducing alterations which are consistent with the symptoms of hyperactivity and impulsivity. In conclusion, due to the complexity of human studies, preclinical investigations in rodent models are necessary for a deeper understanding of ADHD-like symptoms, their neurobiological determinants and their possible modulation by serotonergic manipulations. Further research is essential to increase our knowledge of the psychobiology of ADHD and PG as well as other disorders in which the inhibitory control is compromised.

Impulsivity and gambling proneness in the rat: refinement of innovative methods and manipulation of serotonergic influence / Francesca Zoratto. - STAMPA. - (2012).

Impulsivity and gambling proneness in the rat: refinement of innovative methods and manipulation of serotonergic influence

ZORATTO, FRANCESCA
2012

Abstract

Impulsivity, risk proneness, and poor decision-making are common behavioural symptoms observed in impulse-control disorders, a neuropsychiatric category including attention-deficit/hyperactivity disorder (ADHD) as well as pathological gambling (PG). ADHD, affecting about 3-5% of children, is characterized by traits of inattention, impulsivity, and motor hyperactivity. PG, affecting 0.2-5.3% of adults and 3.5-8.0% of adolescents, is highly comorbid with a range of addictive disorders and is frequently observed in ADHD adolescents and adults. Interest is rising for animal modelling of impaired behavioural inhibition: in order to test the lack of self-control abilities and/or impulsive decision-making, many operant paradigms have been developed, involving a choice with delayed and/or uncertain reinforcers. These choice-based operant tasks, which assess the balance between motivational drives and inhibitory self-control, are extremely useful for investigating reward-discounting processes and their modulation by 5-HT-targeting manipulations. The present thesis is thus focused on the modelling, in laboratory rats, of key symptoms like impulsivity and gambling proneness. Specifically, the first part (chapters 2 and 3) includes a methodological refinement of the operant tasks used, such as Intolerance-to-Delay (ID) and Probabilistic-Delivery (PD) tasks, whereas the second part (chapters 4 and 5) relates to experimental manipulations of the serotonergic influence on these symptoms”. In chapter 2, we report about the marked impact exerted by duration of post-reward timeout (TO) and daily session length (SL) on impulsive choice and gambling proneness in the ID and PD tasks respectively. In chapter 3, we discuss about the role of different methodological improvements in the PD task, implemented (on both the paradigm and the apparatus) to allow testing of adolescent rats in the home-cage, while socially living and within the limited span of this developmental phase. In the fourth chapter, serotonin (5-HT) levels have been manipulated by means of a diet deficient in its precursor, tryptophan (TRP); in the fifth chapter, serotonin transporter (SERT) levels within the hippocampus of rats have been altered through genetic engineering techniques that allow to modulate in-vivo gene expression in specific brain areas. The findings reported in chapter 4 show that TRP depletion leads to changes in behavioural responses related to decision-making as well as a gambling proneness. In chapter 5, we demonstrated that a partial silencing of the SERT-encoding gene is effective in inducing alterations which are consistent with the symptoms of hyperactivity and impulsivity. In conclusion, due to the complexity of human studies, preclinical investigations in rodent models are necessary for a deeper understanding of ADHD-like symptoms, their neurobiological determinants and their possible modulation by serotonergic manipulations. Further research is essential to increase our knowledge of the psychobiology of ADHD and PG as well as other disorders in which the inhibitory control is compromised.
Walter Adriani, Giovanni Laviola
Francesca Zoratto
File in questo prodotto:
File Dimensione Formato  
Thesis Zoratto F.pdf

Accesso chiuso

Tipologia: Tesi di dottorato
Licenza: DRM non definito
Dimensione 5.78 MB
Formato Adobe PDF
5.78 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in FLORE sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2158/806276
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact