Neurobiological and behavioural studies of individual variation in cue-evoked motivation across rodents and humans

Colom, Morgane (2023). Neurobiological and behavioural studies of individual variation in cue-evoked motivation across rodents and humans. PhD thesis The Open University.

DOI: https://doi.org/10.21954/ou.ro.000162bc

Abstract

For a subset of individuals known as sign-trackers, discrete pavlovian cues associated with rewarding stimuli can acquire incentive properties in their own right. When they do so, cues have the ability to exert control over behaviour, which appears to contribute to specific sets of symptoms within neuropsychiatric conditions such as substance use disorder or post-traumatic stress disorder.

Characterising the neurobiological mechanisms mediating variation in cue responsivity is essential to better understand differences in the susceptibility to such disorders. Converging evidence points towards the involvement of dopaminergic neurotransmission in the nucleus accumbens core in the development of sign-tracking; yet, whether this phenotype is associated with specific accumbal postsynaptic properties is unknown. The first section of this thesis investigated the morphology of dendritic spines, presynaptic and postsynaptic markers of activity in the nucleus accumbens core of male and female rats following a pavlovian conditioned approach procedure. Results suggest that individuals who attributed the most incentive salience to a food cue displayed unique dendritic spine organisation; such observations were modulated by the presence or absence of reward. The influence of the oestrous cycle and the altering of sign-tracking by propranolol were also examined.

Developing transitional tools to detect sign-tracking in humans might provide a valuable means to identify profiles conferring vulnerability to maladaptive behaviours. The second section of this thesis describes responses of male and female participants in a computerised image-based pavlovian procedure, a virtual room-based pavlovian environment, and a ‘real-life’ pavlovian procedure in which participants physically interacted with the apparatus. The second and third approaches enabled the development of distinct conditioned phenotypes. Because rodent sign-trackers are more impulsive, the relationship between phenotypes and impulsivity was also considered.

This thesis provides further insight into the neural underpinnings of motivated behaviours and offers guidance for future translational investigation.

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