D_2/3 Agonist during Learning Potentiates Cued Risky Choice

Area of Science:

• Neuroscience
• Behavioral Science
• Pharmacology

Background:

• Dopamine agonist therapies for Parkinson's disease are linked to impulse control and gambling disorders.
• The underlying cognitive and neurobiological mechanisms remain unclear.
• Reward-associated cues can potentiate risky decision-making via the dopamine system.

Purpose of the Study:

• To investigate how ropinirole, a dopamine agonist, affects risk-taking behavior in a cued gambling task.
• To elucidate the neurobiological mechanisms linking dopamine therapy, cues, and risky decision-making.

Main Methods:

• Male rats were treated with ropinirole during acquisition of a cued or uncued rat gambling task (rGT).
• Behavioral analyses assessed impulsivity and choice patterns (risk preference).
• Ex vivo cFos imaging and network analyses examined neural activity in dopaminergic pathways (midbrain, VTA, nucleus accumbens, prefrontal cortex).

Main Results:

• Ropinirole increased risky choices and win-stay behavior during acquisition of the cued rGT, but not the uncued rGT.
• Both ropinirole and win-paired cues suppressed dopaminergic midbrain neuron activity.
• Ropinirole induced decoupling of VTA and nucleus accumbens dopamine neurons specifically in the presence of cues.
• The ratio of midbrain to prefrontal dopamine neuron activity predicted risk preference.

Conclusions:

• Dopamine agonist therapy, particularly with reward-associated cues, can enhance model-free learning and promote risky decision-making.
• Ropinirole may exacerbate gambling disorder risk by disrupting the dopaminergic teaching signal to the prefrontal cortex in a cue-dependent manner.
• Altered frontostriatal network dynamics, driven by dopamine system changes and cue-potentiated learning, underlie therapy-induced behavioral changes.