Doctoral thesis

Environmental and dopaminergic factors associated with impulsivity and novelty seeking: implications for substance abuse

ContributorsBelles Ano, Lidia
Number of pages192
Imprimatur date2022-11-08
Defense date2022-11-08

Understanding how individuals who have a greater propensity to abuse drugs differ from those who are less so represents a major challenge in addiction research. Current research suggests a neurobehavioral endophenotype conferring vulnerability to drug abuse. Particularly, high impulsivity and high novelty-seeking have been linked to alterations in dopamine (DA) signaling with the mesostriatal system, and notably, to a deficit in striatal DA D2/3 receptor (D2/3R). However, the vast majority of studies investigating the neurobiological underpinnings of impulsivity and novelty-seeking have focused on post-synaptic D2/3R, and few studies have investigated presynaptic aspects of DA signaling, such as presynaptic DA release, albeit it is known to regulate postsynaptic D2/3R expression. Furthermore, it appears that environmental and social factors can influence these personality and neurochemical variables and ultimately the propensity to drug abuse. More research is, however, needed to determine whether environmental-related changes in D2/3R availability and/or presynaptic capacity to release DA represent, at least in part, the molecular mechanism underlying the interaction between environment and predisposition to drug abuse. Besides, impulsivity is a multidimensional construct encompassing impulsive action and impulsive choice. Although there is a high comorbidity between these constructs of impulsivity in psychiatric disorders such as drug addiction and pathological gambling, there have been no clear demonstrations that these are associated in the normal population. Moreover, given the wealth of studies supporting a central role of DA in all constructs of impulsivity, investigating their underlying dopaminergic underpinnings was a logical lead to explore for understanding the neurochemical substrates of impulsive behaviors. Therefore, in the present thesis, I studied the predictive value of striatal D2/3R density and capacity to release DA on impulsivity and novelty seeking, and further assessed the influence of environmental enrichment or impoverishment on these neurobiological traits and the propensity to drug abuse later in life. In addition, the relationships between the different constructs of impulsivity and their respective underlying dopaminergic underpinnings in a normal population were examined. The first study of my thesis revealed that while impulsivity and novelty preference are interrelated and co-segregate with similar pre- and postsynaptic indices of striatal DA function, both behavioral traits depend on overlapping but not identical DA-dependent mechanisms in striatum. More specifically, I observed that impulsivity is directly related to both a reduced striatal D2/3R availability and heightened capacity to evoke DA release, while novelty preference is mainly related to the latter. In the second study, data revealed that environmental impoverishment was strongly associated with decreased drug-seeking behaviors in “addiction-prone” rats, thus suggesting that impoverished environments likely decrease the reinforcing effects of psychostimulants, attenuating, rather than potentiating, the propensity to develop drug abuse later in life in predisposed individuals. Moreover, our data also revealed the existence of non-monotonic, environment-dependent, relationships between addiction-related

  • Dopamine
  • Impulsivity
  • Novelty preference
  • D2 receptors
  • Environmental enrichment
  • Environmental impoverishment
  • Dopamine release
  • Cocaine
  • Delay discounting
  • Impulsive action
  • Impulsive choice
  • Risky decision-making
  • Dopamine receptors
  • Baseline-dependent
Citation (ISO format)
BELLES ANO, Lidia. Environmental and dopaminergic factors associated with impulsivity and novelty seeking: implications for substance abuse. 2022. doi: 10.13097/archive-ouverte/unige:165947
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Creation11/17/2022 8:27:00 AM
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