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Gambling disorder (GD) is a behavioral addiction characterized by persistent and recurrent gambling behavior that disrupts personal, social or professional life. Studies have revealed that GD shares many features with alcohol and substance use disorders, but little is known about potential unique features in GD and to what extent characteristics are shared. One shared feature is reward-related decision-making and individuals with GD display deficits in decision-making. The rat gambling task (rGT) has been developed to enable preclinical studies of reward-related decision-making and underlying neurobiological mechanisms.

The aim of this thesis was to explore individual differences in decision-making strategies in the rGT and underlying behavioral phenotypes and neurobiology.

Paper I: three groups with different decision-making strategies in the rGT were identified: the strategic, risky and safe group. The rGT strategies were shown to be stable over time, even after multiple interruptions and other behavioral testing. Rats with risky rGT strategies had higher voluntary alcohol intake but not elevated sexual behavior. Naltrexone treatment resulted in an overall lowered motivation in the rGT but had no effect on choice behavior.

Paper II: individual differences in gambling strategies were found in the rGT and corresponding strategy groups were replicated from Paper I. Moreover, brain functional connectivity was assessed using resting-state functional Magnetic Resonance Imaging. Differences in rGT strategies were associated with connectivity in regions in or associated with brain reward networks.

Paper III: levels of neurotransmitters and metabolites were explored using matrix-assisted laser desorption/ionization mass spectrometry imaging in selected brain regions. The strategy groups were revealed to differ in levels of neurotransmitters and metabolites in regions of importance for decision-making and reward.

Paper IV: decision-making strategies in humans, using the Iowa gambling task, and in rats, using the rGT, were explored. Results showed that most humans and rats learned to favor the advantageous choices and showed similar variability in individual choice preferences during end performance.

This thesis has provided new information about individual decision-making strategies in the rGT and associations with other reward-related behaviors as well as neurobiology. Characterization of the strategy groups indicates a shared underlying mechanism between rGT strategies and alcohol intake but not natural rewards. Neurobiological differences in regions important for reward processing were also revealed. Lastly, similar variability in individual choice preference was found in humans and rats and it is concluded that both clinical and preclinical research would benefit from more detailed analyses on individual variations in decision-making.

This thesis investigated autonomic responses and decision-making during two gambling tasks in a population of young adults. The included papers specifically addressed: 1) autonomic responses and subjective perceptions of slot machine outcomes, with a focus on the effects of near-misses; 2) decision-making strategies in human and animal gambling tasks; and 3) differential autonomic responsivity during gambling and decision-making as a function of polymorphic variants of the dopamine D2 receptor (Taq1A and C957T), including potential influences of prior gambling exposure and sex.  

The four papers were based on data from an experimental study conducted at Västmanland Hospital in Västerås, Sweden. Participants (n = 270) completed two gambling tasks—a slot machine gambling task and the Iowa Gambling Task (IGT)—while their heart rate (HR) and skin conductance responses (SCR) were simultaneously recorded. Saliva samples were collected for DNA extraction. Additionally, Paper II included comparisons with adult outbred male Lister Hooded rats (N = 72) performing the rat Gambling Task (rGT).

Findings from Paper I contribute to the existing literature on the near-miss effect in gambling, demonstrating heightened autonomic responses to these structural features, along with distinct subjective perceptions of affect, motivation, and perceived chances of winning across different near-miss subtypes. Furthermore, females exhibited stronger responses to winning outcomes compared to males.

Comparisons of decision-making strategies in the IGT and rGT in Paper II revealed that human performance was characterized by exploration and learning over time, whereas rats displayed relatively stable preferences for advantageous choices throughout the task. Procedural differences in task protocols suggest that these models are suited to examining distinct aspects of decision-making.

Papers III and IV provide preliminary evidence that polymorphic variants of the D2 dopamine receptor are associated with differential autonomic sensitivity to slot machine gambling cues and rewards, as well as anticipatory responses linked to implicit guidance during decision-making under uncertainty. These relationships were further influenced by prior gambling exposure and sex, suggesting potential differential susceptibility to gambling stimuli.

In conclusion, near-misses should be considered in gambling regulation policies aimed at harm prevention. Translational inferences from both human and animal studies require careful methodological considerations and to what degree they capture similar psychological constructs that are relevant to real-world gambling behaviors. Furthermore, potential gene-environment interactions between genetic predispositions and gambling exposure in shaping emotional responses and decision-making warrant further investigation in well-powered studies.