This study aims to investigate the efficacy of electrical stimulation by comparing network-mediated RGC responses in normal and degenerate retinas using a N-methyl-N-nitrosourea (MNU)-induced non-human primate (NHPs) retinitis pigmentosa (RP) model. Adult cynomolgus monkeys were used for normal and outer retinal degeneration (RD) induced by MNU. The network-mediated RGC responses were recorded from the peripheral retina mounted on an 8 × 8 multielectrode array (MEA). The amplitude and duration of biphasic current pulses were modulated from 1 to 50 μA and 500 to 4000 μs, respectively. The threshold charge density for eliciting a network-mediated RGC response was higher in the RD monkeys than in the normal monkeys (1.47 ± 0.13 mC/cm2 vs. 1.06 ± 0.09 mC/cm2, p < 0.05) at a 500 μs pulse duration. The monkeys required a higher charge density than rodents among the RD models (monkeys; 1.47 ± 0.13 mC/cm2, mouse; 1.04 ± 0.09 mC/cm2, and rat; 1.16 ± 0.16 mC/cm2, p < 0.01). Increasing the pulse amplitude and pulse duration elicited more RGC spikes in the normal primate retinas. However, only pulse amplitude variation elicited more RGC spikes in degenerate primate retinas. Therefore, the pulse strategy for primate RD retinas should be optimized, eventually contributing to retinal prosthetics. Given that RD NHP RGCs are not sensitive to pulse duration, using shorter pulses may potentially be a more charge-effective approach for retinal prosthetics.
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.