Altered prefrontal dopaminergic function in chronic recreational ketamine users

Area of Science:

• Neuroscience
• Psychiatry
• Radiology

Background:

• Ketamine, an NMDA receptor antagonist, is used medically but increasingly abused recreationally.
• Chronic ketamine use's effects on the human brain, particularly the prefrontal dopaminergic system, are not well understood.
• Animal studies suggest vulnerability of the prefrontal dopaminergic system to NMDA antagonists.

Purpose of the Study:

• To assess dopamine D1 receptor availability in chronic recreational ketamine users.
• To investigate the impact of ketamine abuse on the human brain's prefrontal dopaminergic system.

Main Methods:

• Positron emission tomography (PET) with the radioligand [11C]NNC 112 was used to measure D1 receptor availability.
• Hair analysis confirmed ketamine abuse history.
• Kinetic analysis with arterial input function quantified [11C]NNC 112 binding potential.

Main Results:

• Dopamine D1 receptor availability was significantly up-regulated in the dorsolateral prefrontal cortex of chronic ketamine users compared to controls.
• No significant differences in D1 receptor availability were found in other brain regions.
• Up-regulation of D1 receptors in the prefrontal cortex correlated with the weekly amount of ketamine used.

Conclusions:

• Chronic ketamine users show increased D1 receptor availability in the dorsolateral prefrontal cortex, similar to findings after dopamine depletion in animal models.
• Recreational ketamine use impacts prefrontal dopaminergic transmission.
• This disruption affects critical functions like working memory and executive function.