Negative Urgency Exacerbates Relapse to Cocaine Seeking After Abstinence

Area of Science:

• Neuroscience
• Behavioral Science
• Addiction Research

Background:

• Mechanisms of drug relapse, particularly drug-cue-induced negative affective states, remain unclear.
• Investigating the role of negative urgency in relapse severity.
• Understanding the neural underpinnings of cue-controlled cocaine-seeking habits.

Purpose of the Study:

• To test the hypothesis that loss of opportunity to perform a dorsolateral striatum (DLS)-dependent cocaine-seeking habit during abstinence exacerbates relapse.
• To determine if relapse is driven by withdrawal or the inability to perform the drug-seeking response.
• To investigate the striatal systems involved in cocaine seeking and relapse.

Main Methods:

• Trained rats to seek cocaine using drug-associated cues.
• Assessed relapse tendency in relation to withdrawal state versus opportunity to perform the habit.
• Used C-fos expression and dopamine receptor blockade to examine striatal control (dorsomedial striatum vs. DLS) over drug seeking.

Main Results:

• A DLS-dependent cue-controlled cocaine-seeking habit led to increased relapse.
• Relapse was not motivated by cocaine withdrawal.
• Relapse was driven by negative urgency from prevented habit performance, involving transient goal-directed system engagement.

Conclusions:

• Ingrained cue-controlled drug-seeking habits significantly increase the urge to relapse.
• The inability to perform established drug-seeking habits during abstinence is a key factor in relapse severity.
• Negative urgency, stemming from habit performance prevention, plays a critical role in addiction relapse.