LSD persistently disrupts affective pain processing.

Area of Science:

• Neuroscience
• Psychopharmacology

Background:

• Psychedelics induce lasting effects, but their underlying neural circuit mechanisms are not fully understood.
• Investigating the neural basis of psychedelic action is crucial for understanding their therapeutic potential.

Purpose of the Study:

• To elucidate the circuit mechanisms by which lysergic acid diethylamide (LSD) produces long-lasting reductions in pain affect.
• To determine the role of the anterior cingulate cortex (ACC) in mediating the anti-nociceptive effects of LSD.

Main Methods:

• Administered a single dose of LSD to rats and assessed long-term changes in pain affect.
• Used local administration of LSD in specific brain regions, including the ACC and primary somatosensory cortex.
• Performed Neuropixels recordings to analyze neuronal responses in the ACC before and after LSD administration.
• Examined neuronal excitability ex vivo and in vivo.

Main Results:

• LSD persistently reduced pain affect in rats.
• Local administration of LSD in the ACC, but not the primary somatosensory cortex, mimicked this effect.
• LSD suppressed stimulus-evoked nociceptive responses in the ACC, diminishing the encoding of aversive value.
• A dissociation was observed between increased intrinsic excitability ex vivo and reduced stimulus-evoked firing in vivo.

Conclusions:

• LSD disrupts the cortical processing of nociceptive input, specifically altering the transformation into aversive representations within the ACC.
• These findings highlight the ACC as a key circuit mediating the long-lasting anti-nociceptive effects of psychedelics.