Renewal of extinguished cocaine-seeking

Area of Science:

• Neuroscience
• Behavioral Neuroscience
• Addiction Research

Background:

• Relapse to drug seeking remains a significant challenge in addiction treatment.
• Understanding the neural circuits underlying relapse is crucial for developing effective interventions.
• Context-dependent renewal of drug seeking is a well-established phenomenon in preclinical models.

Purpose of the Study:

• To investigate the neural substrates of context-dependent renewal of cocaine seeking behavior in rats.
• To identify specific brain regions and neuronal populations involved in the renewal of extinguished cocaine self-administration.
• To differentiate the neural pathways involved in renewal from those associated with general drug-seeking responses.

Main Methods:

• Rats were trained to self-administer cocaine and then extinguished in a different context.
• Cocaine seeking was tested in the original or a novel context to induce renewal.
• c-Fos immunohistochemistry and retrograde tracing techniques were used to map neuronal activity and connectivity.

Main Results:

• Renewal of cocaine seeking (group ABA) was associated with c-Fos expression in the basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex.
• General test-associated c-Fos induction occurred in prelimbic prefrontal cortex, nucleus accumbens, striatum, lateral amygdala, perifornical hypothalamus, and ventral tegmental area.
• Renewal-specific c-Fos in the lateral hypothalamus was orexin-negative, while test-associated c-Fos in the perifornical hypothalamus was orexin-positive.

Conclusions:

• Renewal of cocaine seeking critically depends on the basolateral amygdala, lateral hypothalamus, and infralimbic prefrontal cortex.
• These brain regions contribute to renewal independently of their projections to the lateral hypothalamus or ventral tegmental area.
• Infralimbic prefrontal cortex involvement appears unique to cocaine seeking renewal, potentially reflecting habitual drug use.