Hallucinogens have been prescribed for the treatment of mental illnesses; however, reports on the dependence potential of hallucinogens across species remain inconsistent. Non-human primate (NHP) self-administration model are suitable for evaluating species-specific reinforcement behavior induced by hallucinogens. In this study, we demonstrated that 4-bromo-2,5-dimethoxyphenethylamine (2C-B) was self-administered orally in freely moving marmoset (Callithrix jacchus). 2C-B-treated mice did not demonstrate reinforcement behavior in self-administration paradigm as well as brain stimulation behavior in intracranial self-stimulation (ICSS) test. Interestingly, 2C-B-induced dopamine neuronal activity was demonstrated only in the brain of marmosets as evidenced by fluorescent false neurotransmitter assessment and measurement of synaptosome dopamine levels. We sought to study possible molecular mechanisms underlying this and docking simulations revealed that 2C-B occupied a binding pocket overlapping the canonical dopamine-binding site in both species but adopted a distinct interaction pattern in marmoset DAT involving Leu321. Pull-down assays demonstrated stronger DAT-associated 2C-B binding in marmosets than in mice. Furthermore, 2C-B produced greater inhibition of DAT-mediated FFN102 uptake in cells expressing marmoset or human DAT than in cells expressing mouse DAT, whereas substitution of Leu321 abolished this effect. Collectively, these findings demonstrate that 2C-B induces reward-related behaviors in marmosets and identify species-specific DAT-2C-B interactions as a potential mechanism underlying differential dopaminergic and behavioral responses across species.

Two male marmosets underwent vasectomy without complications. Azoospermia was confirmed by computer‐assisted semen analysis (CASA) 5 weeks later. Both were co‐housed with embryo transfer recipient females 6 weeks after surgery. Vasectomy may be accompanied by post‐vasectomy semen analysis such as CASA, to ensure safe and reliable sterilization for research and captive breeding management in marmosets.

To date, no pharmacotherapy has been approved for cocaine use disorder. Endocannabinoid signaling is closely related to dopamine-dependent reinforcement and may regulate cocaine-related behaviors. In this study, we used common marmosets ( Callithrix jacchus ) to investigate whether 2-arachidonoylglycerol (2-AG), an endogenous cannabinoid lipid, reduces cocaine reinforcement in a non-restraint oral self-administration model. Marmosets performed oral cocaine self-administration under a fixed-ratio 1 schedule, and cocaine intake was confirmed using plasma benzoylecgonine detection. Dopamine transporter (DAT)-related positron emission tomography (PET) signal, DAT and G protein-coupled receptor 55 (GPR55)- associated fluorescent signals, GPR55/DAT immunofluorescence, and synaptosomal dopamine responses were assessed using 18F-N-(3-fluoropropyl)-2β-carboxymethoxy-3β-(4-iodophenyl) nortropane ( ¹⁸ F-FP-CIT) PET imaging, ex vivo fluorescent ligand imaging, confocal microscopy, and dopamine quantification. Marmosets acquired oral cocaine self-administration with preferential active lever responding. Repeated cocaine self-administration reduced striatal DAT-related ¹⁸ F-FP-CIT PET signal in vivo. In striatal slices, cocaine decreased fluorescent false neurotransmitter (FFN102)-associated DAT signal and increased T1117-associated GPR55 signal. Systemic 2-AG pretreatment reduced cocaine self-administration while restoring diminished circulating 2-AG levels. GPR55 and DAT immunofluorescent signals were colocalized in marmoset brain sections, and 2-AG enhanced cocaine-induced dopamine elevation in synaptosomal preparations. Taken together, these findings suggest that 2-AG attenuates cocaine-taking behavior and may be associated with GPR55/DAT-related dopaminergic responses in common marmosets.

As the use of the common marmoset (Callithrix jacchus) expands in biomedical research, knowledge gaps persist in the management of parasitic gastrointestin