Associations between dopaminergic and serotonergic systems in individuals with cocaine use disorder: An exploratory analysis of [¹¹C]PHNO and [¹¹C]P943 PET imaging.
case_series · Level IV
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- Record sourced from PubMed, PMID 42685387.
- Also identified by DOI 10.1016/j.drugalcdep.2026.113329.
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Abstract
[¹ ¹C]PHNO is a positron emission tomography (PET) radioligand for dopamine D<sub>2</sub>/D<sub>3</sub> receptors (D<sub>2</sub>R/D<sub>3</sub>R), while [¹ ¹C]P943 selectively targets 5-HT<sub>1B</sub> receptors. Although prior studies have shown differences in dopaminergic and serotonergic receptor availability in people with and without cocaine use disorder (CUD), these systems have been examined in isolation across separate studies and samples. Ten non-treatment-seeking individuals with CUD (3 women; mean [SD] age, 40.6 [7.5] years) underwent PET imaging with [¹ ¹C]PHNO and [¹ ¹C]P943 following an average of 7 ± 3 days of abstinence under inpatient monitoring. Availability of D<sub>2</sub>R- and D<sub>3</sub>R-related receptors was measured with [¹ ¹C]PHNO binding potentials (BP<sub>ND</sub>) in the putamen and substantia nigra/ventral tegmental area (SN/VTA), respectively. Exploratory linear regression analyses using both D<sub>2</sub>R- and D<sub>3</sub>R-related receptor availability as independent variables were applied to 5-HT<sub>1B</sub>BP<sub>ND</sub> in the medial orbitofrontal cortex (mOFC) and dorsomedial prefrontal cortex (dmPFC), with secondary analyses examining the same dopaminergic-serotonergic associations in additional addiction-related prefrontal regions. D<sub>2</sub>R-related receptor availability was positively associated with 5-HT<sub>1B</sub>BP<sub>ND</sub> in the dmPFC (p = 0.038) but not in the mOFC (p = 0.945). Conversely, D<sub>3</sub>R-related receptor availability was positively associated with 5-HT<sub>1B</sub>BP<sub>ND</sub> in the mOFC (p = 0.043) but not in the dmPFC (p = 0.850). Analyses of secondary 5-HT<sub>1B</sub> regions revealed a positive association between D<sub>3</sub>R-related receptor availability and 5-HT<sub>1B</sub>BP<sub>ND</sub> in the lateral OFC (lOFC) (p = 0.050). In individuals with CUD, D<sub>2</sub>R- and D<sub>3</sub>R-related measures were associated with 5-HT<sub>1B</sub> binding in distinct prefrontal regions. These findings provide preliminary in vivo evidence of cross-system dopaminergic-serotonergic relationships and may inform future development efforts toward targeted treatments for CUD.