Spännande läkemedelsforskning

Abstract

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.