Neuropharmacology
September 1, 2024
Devin P Hagarty, Adam Dawoud, Alfonso Brea Guerrero et al.
6 citations
Ketamine, used for treatment-resistant depression, shows reinforcing effects in both male and female rats at higher doses (0.25 and 0.5 mg/kg/infusion), with females self-administering more at the highest dose. All doses that supported self-administration led to cue-induced reinstatement. After reinstatement, ketamine-treated animals had higher cFos protein expression in the nucleus accumbens than saline controls, with greater expression in the core than shell subregion, and no sex differences in this neural activation. These dose- and sex-dependent effects highlight the need for further research into ketamine's addictive potential, especially at lower clinical doses.
eNeuro
March 1, 2025
Sarah D Jennings, Devin P Hagarty, Jordan Logue et al.
1 citation
Repeated ketamine infusions for depression may be riskier in people with a history of alcohol use, and effects differ by sex. In rats, females self-administered more ketamine than males. A history of alcohol increased ketamine intake in females, while a history of either isolation or alcohol independently increased ketamine intake in males. All groups showed similar extinction and cue-induced reinstatement. In the nucleus accumbens, isolation increased immature dendritic spines in males, an effect reduced by alcohol; alcohol increased immature spines in females. The findings suggest that prior social isolation and alcohol exposure alter ketamine's reinforcing properties in a sex-dependent manner, highlighting the need to consider sex and alcohol history when using ketamine to treat depression.
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.