Role of accumbens medium spiny neurons subtypes in reinstatement to ketamine cues in male and female Long Evans rats.
Neuropharmacology June 6, 2026 Devin P. Hagarty, Adam Dawoud, Alfonso Brea Guerrero et al.
Ketamine is approved for treatment-resistant depression and is being tested for substance use disorder and PTSD, but its addictive potential raises safety concerns. The nucleus accumbens (NAc), a brain reward hub, is involved in how drug-related cues become salient. The NAc contains two types of medium spiny neurons (MSNs): those expressing dopamine 1 receptors (D1R) and those expressing dopamine 2 receptors (D2R). Using DREADD technology in transgenic rats, the authors found that D1R-expressing MSNs, but not D2R-expressing ones, play a key role in reinstatement of seeking behavior triggered by ketamine-associated cues. This identifies a cell-type specific mechanism in ketamine's addictive properties.