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.