Cocaine increases stimulation-evoked serotonin efflux in the nucleus accumbens

Jason Yuen, Abhinav Goyal, Aaron E. Rusheen, Abbas Z. Kouzani, Michael Berk, Jee Hyun Kim, Susannah J. Tye, Charles D. Blaha, Kevin E. Bennet, Kendall H. Lee, Yoonbae Oh, Hojin Shin

Research output: Contribution to journalArticlepeer-review


Although dopamine is the most implicated neurotransmitter in the mediation of the pathophysiology of addiction, animal studies show serotonin also plays a vital role. Cocaine is one of the most common illicit drugs globally, but the role of serotonin in its mechanism of action is insufficiently characterized. Consequently, we investigated the acute effects of the psychomotor stimulant cocaine on electrical stimulation-evoked serotonin (phasic) release in the nucleus accumbens core (NAcc) of urethane-anesthetized (1.5 g/kg ip) male Sprague-Dawley rats using N-shaped fast-scan cyclic voltammetry (N-FSCV). A single carbon fiber microelectrode was first implanted in the NAcc. Stimulation was applied to the medial forebrain bundle using 60 Hz, 2 ms, 0.2 mA, 2- s biphasic pulses before and after cocaine (2 mg/kg iv) was administered. Stimulation-evoked serotonin release significantly increased 5 min after cocaine injection compared with baseline (153 ± 21 nM vs. 257 ± 12 nM; P = 0.0042; n = 5) but was unaffected by saline injection (1 mL/kg iv; n = 5). N-FSCV's selective measurement of serotonin release in vivo was confirmed pharmacologically via administration of the selective serotonin reuptake inhibitor escitalopram (10 mg/kg ip) that effectively increased the signal in a separate group of rats (n = 5). Selectivity to serotonin was further confirmed in vitro in which dopamine was minimally detected by N-FSCV with a serotonin to dopamine response ratio of 1:0.04 (200 nM of serotonin:1 mM dopamine ratio; P = 0.0048; n = 5 electrodes). This study demonstrates a noteworthy influence of cocaine on serotonin dynamics, and confirms that N-FSCV can effectively and selectively measure phasic serotonin release in the NAcc.

Original languageEnglish (US)
Pages (from-to)714-724
Number of pages11
JournalJournal of neurophysiology
Issue number3
StatePublished - Mar 2022


  • addiction
  • cocaine
  • nucleus accumbens
  • serotonin
  • voltammetry

ASJC Scopus subject areas

  • Neuroscience(all)
  • Physiology


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