(+)-Catharanthine and (-)-18-methoxycoronaridine induce antidepressant-like activity in mice by differently recruiting serotonergic and norepinephrinergic neurotransmission

Arias, Hugo R.; Deurwaerdère, Philippe De; El‐Kasaby, Ali; Giovanni, Giuseppe Di; Eom, Sanung; Lee, Junho H; Freissmuth, Michael; Chagraoui, Abdeslam

doi:10.1016/j.ejphar.2022.175454

Cited by 6 publications

(5 citation statements)

References 42 publications

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“…We additionally tested the effect of 18-MC on DA uptake and found that it had no significant effect on tau or downward velocity, suggesting it has low affinity for the DAT (Figure ). These results are in confirmation with our recent work showing that catharanthine inhibits the DAT, as well as the norepinephrine and serotonin transporters …”

Section: Discussionsupporting

confidence: 93%

“…Based on our results showing increases in extracellular DA, its mechanism of action through striatal nAChRs in modulating DA release, and our previous work showing differential antidepressant effects of catharanthine and 18-MC in mice, we hypothesized that catharanthine would attenuate NIC-induced hyperlocomotion and SA in rats. Despite previous results showing that 18-MC does not inhibit NIC-induced locomotor activity, we found that both catharanthine and 18-MC inhibited NIC-induced hyperlocomotion in rats in a dose-dependent manner (Figure ).…”

Section: Discussionmentioning

confidence: 93%

“…Analysis of the time and velocity of the falling edge of the voltammetric DA release curve can reveal the level of DA reuptake mediated by the DA transporter (DAT). While catharanthine and 18-MC are known to inhibit monoamine transporters with different affinities and potencies in vitro , , the effect of catharanthine on endogenous evoked DA release was not known. We hypothesized that catharanthine-induced inhibition of the DAT would result in slowing the falling edge of the DA voltammetric curve, thus increasing extracellular DA levels.…”

Section: Resultsmentioning

confidence: 99%

“…These results are in confirmation with our recent work showing that catharanthine inhibits the DAT, as well as the norepinephrine and serotonin transporters. 28 To better understand the effects of catharanthine on DA dynamics in the brain, we measured extracellular levels of DA in a live animal using microdialysis and HPLC combined with electrochemical detection. In vivo DA release measurements demonstrate what happens to the brain on a systemic level.…”

Section: ■ Discussionmentioning

confidence: 99%

“…26,27 Our recent study showed that catharanthine and 18-MC induce antidepressant-like activity in mice by differentially activating the serotonergic and norepinephrinergic pathways. 28 Previous behavioral studies showed that 18-MC decreases NIC SA in rats 10 and NIC-induced neurochemical, but not locomotor, sensitization. 25 However, no research has investigated the effect of catharanthine on drug-seeking behaviors or on DA transmission.…”

Section: ■ Introductionmentioning

confidence: 98%

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Catharanthine Modulates Mesolimbic Dopamine Transmission and Nicotine Psychomotor Effects via Inhibition of α6-Nicotinic Receptors and Dopamine Transporters

Williams,

Steed,

Woolley

et al. 2024

ACS Chem. Neurosci.

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Iboga alkaloids, also known as coronaridine congeners, have shown promise in the treatment of alcohol and opioid use disorders. The objective of this study was to evaluate the effects of catharanthine and 18-methoxycoronaridine (18-MC) on dopamine (DA) transmission and cholinergic interneurons in the mesolimbic DA system, nicotine-induced locomotor activity, and nicotine-taking behavior. Utilizing ex vivo fast-scan cyclic voltammetry (FSCV) in the nucleus accumbens core of male mice, we found that catharanthine or 18-MC differentially inhibited evoked DA release. Catharanthine inhibition of evoked DA release was significantly reduced by both α4 and α6 nicotinic acetylcholine receptors (nAChRs) antagonists. Additionally, catharanthine substantially increased DA release more than vehicle during high-frequency stimulation, although less potently than an α4 nAChR antagonist, which confirms previous work with nAChR antagonists. Interestingly, while catharanthine slowed DA reuptake measured via FSCV ex vivo, it also increased extracellular DA in striatal dialysate from anesthetized mice in vivo in a dose-dependent manner. Superfusion of catharanthine or 18-MC inhibited the firing rate of striatal cholinergic interneurons in a concentration dependent manner, which are known to potently modulate presynaptic DA release. Catharanthine or 18-MC suppressed acetylcholine currents in oocytes expressing recombinant rat α6/α3β2β3 or α6/α3β4 nAChRs. In behavioral experiments using male Sprague-Dawley rats, systemic administration of catharanthine or 18-MC blocked nicotine enhancement of locomotor activity. Importantly, catharanthine attenuated nicotine self-administration in a dose-dependent manner while having no effect on food reinforcement. Lastly, administration of catharanthine and nicotine together greatly increased head twitch responses, indicating a potential synergistic hallucinogenic effect. These findings demonstrate that catharanthine and 18-MC have similar, but not identical effects on striatal DA dynamics, striatal cholinergic interneuron activity and nicotine psychomotor effects.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 93%