Effects of orbitofrontal cortex lesions on cocaine self-administration

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Addiction Research

Background:

• Limbic and prefrontal cortical areas are implicated in regulating drug-seeking behavior.
• The orbitofrontal cortex (OFC) is a key prefrontal region involved in decision-making and impulse control.

Purpose of the Study:

• To investigate the specific role of the orbitofrontal cortex (OFC) in the acquisition, dose-dependency, patterning, and reinstatement of cocaine self-administration.
• To determine if OFC lesions affect cocaine seeking differently than food-seeking behavior.

Main Methods:

• Rats with orbitofrontal cortex (OFC) or sham lesions underwent cocaine self-administration training.
• Lesions were performed either before or after behavior acquisition.
• Behavioral responses were assessed across various cocaine doses and during extinction and reinstatement tests.
• Parallel experiments assessed the effects of OFC lesions on food-reinforced responding.

Main Results:

• OFC lesions before acquisition accelerated cocaine self-administration acquisition and increased responding at low doses.
• Lesions after acquisition led to a significant increase (approx. 250%) in responding at the lowest dose, with increased timeout responding and drug loading.
• Pre-acquisition OFC lesions did not affect cocaine-induced reinstatement but accelerated extinction of food-reinforced responding.
• OFC lesions did not alter acquisition, maintenance, or reinstatement of food-reinforced responding.

Conclusions:

• OFC lesions enhance cocaine self-administration, particularly at low doses, suggesting impaired response inhibition or reward value tracking.
• The effects of OFC lesions on drug-seeking behavior differ from those observed in long-access addiction models.
• The OFC plays a critical role in regulating the inhibition of drug-seeking behavior and potentially in the valuation of drug-related cues.