Poster De Conférence Année : 2023

Distinct roles played by dopamine and serotonin systems in approach-avoidance behavior: a pharmacological study associated with PET imaging in non-human primate.

Résumé

Approaching pleasant, positive stimuli and avoiding unpleasant, negative ones is a core element of adaptive behavior in response to important, emotionally stimuli. Biased approach-avoidance behaviors are a hallmark of many psychiatric disorders such as anxiety and impulsive disorders. To regulate appetitive and aversive motivational states involved in these types of behaviors, the positive or negative valence is thought to be regulated by the dopamine (DA) and serotonin (5-HT) systems. However, the specific roles played by DA and 5-HT in approach-avoidance tendencies remain unclear. Some studies suggest distinct involvement, while others describe a combined regulation of approach-avoidance behaviors by both DA and 5-HT systems. To address this issue, we compared the effects of DA or 5-HT manipulation in 4 macaques trained to perform an approach-avoidance task in which they had to adapt their behavior depending on the valence of visual stimuli. We increased synaptic dopamine levels by injections of methylphenidate (MPH) (0.1 mg/kg), while 5-HT levels were selectively boosted by injections of fluoxetine (FLX) (4 mg/kg). In addition, we conducted PET scans with [11C]PE2I or [11C]DASB to identify where in the brain these two reuptake inhibitors acted to modulate DA/5-HT systems and further affect monkeys’ choice. Consistent with a selective role of DA in regulating approach responses, monkeys exposed to MPH showed an increase in the willingness to work to get rewards and few effects on aversive condition. Combined with PET imaging, our results suggest a specific role of DA in the processing of positive information within the anterior striatum. Monkeys exposed to FLX showed a better self-control and task engagement in aversive condition, when animals had to avoid the air-puffs. These drug-induced effects indicate a stronger involvement of 5-HT system in regulating the processing of negative information required to drive avoidance behavior. In PET results, the neural network supporting this negative valence system appears to be larger distributed between the limbic cortical regions and the anterior striatum. Hence, in addition to a key role in appetitive processing modulated by the DA system, our results shed light on the involvement of the anterior striatum in aversive processing modulated by the 5-HT system. Together, DA and 5-HT systems appear to play complementary roles in the control of motivational states involved in approach-avoidance behaviors.

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hal-04983914 , version 1 (09-03-2025)

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  • HAL Id : hal-04983914 , version 1

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Léon Tremblay, Lisa Gauthier, Guillaume Drui, Justine Debatisse, Yosuke Saga, et al.. Distinct roles played by dopamine and serotonin systems in approach-avoidance behavior: a pharmacological study associated with PET imaging in non-human primate.. NeuroFrance, May 2023, Lyon, France. ⟨hal-04983914⟩
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