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The anxiogenic drug yohimbine is a reinforcer in male and female rats

Neuropsychopharmacology volume 50, pages 432–443 (2025)Cite this article

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A Correction to this article was published on 31 January 2025

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Abstract

The indole alkaloid yohimbine is an anxiogenic drug that activates stress-responsive systems in the brain. However, because yohimbine also elicits approach behaviors, this study employed male and female Sprague-Dawley rats to explore its potential reinforcing effects. Thus, it was first determined if intravenous (IV) infusions of yohimbine (0.25 mg/kg/infusion) could maintain lever pressing, whether intake could be modulated by dose/infusion, and if lever pressing would persist in the absence of yohimbine or yohimbine-paired cues. Next, to assess yohimbine’s effect on memory consolidation, 0.3, 1.25 or 3 mg/kg yohimbine was administered post-training using an object recognition memory task. Finally, place conditioning assessed whether doses of yohimbine that elevate blood serum corticosterone levels (1.25 or 3 mg/kg) could elicit a conditioned place preference. It was found that both sexes acquired yohimbine IV self-administration, that intake was modulated by dose/infusion, and that lever pressing persisted during extinction and in the absence of the yohimbine-paired cue. As well, post-training injections of 1.25 mg/kg yohimbine enhanced consolidation of object memory, and 1.25 and 3 mg/kg elevated corticosterone levels and elicited a place preference in both sexes. Finally, in behavioral tests of psychomotor functions, acute yohimbine increased lever pressing for a visual cue and elevated locomotor activity. These findings reveal a profile of yohimbine’s behavioral effects that is consistent with that of psychostimulant reinforcing drugs.

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Fig. 1: Both sexes acquired intravenous self-administration of yohimbine, intake was modulated by dose per infusion, and responding persisted during extinction and in the absence of the yohimbine-paired cue.
Fig. 2: Intravenous yohimbine doses produce different cumulative records of active lever presses during  self-administration and extinction sessions.
Fig. 3: Yohimbine enhances consolidation of object recognition memory and lever pressing for a sensory stimulus.
Fig. 4: Yohimbine doses that elevate blood serum corticosterone levels elicit conditioned place preference.

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Data are provided as supplementary material.

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Funding

This work was supported by the Natural Sciences and Engineering Research Council of Canada to FL. The funding source had no role in study design; data collection, analyses, or interpretation; writing; or decision to submit article for publication.

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  1. Department of Psychology and Collaborative Neuroscience Program, University of Guelph, Guelph, ON, Canada

    Briana Renda & Francesco Leri

  2. Department of Psychology, University of Toronto, Scarborough, ON, Canada

    Francesco Leri

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  1. Briana Renda
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  2. Francesco Leri
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BR was responsible for conception, execution of all experiments, data analysis, and writing of manuscript. FL contributed to data analysis and co-wrote manuscript.

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Correspondence to Francesco Leri.

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Renda, B., Leri, F. The anxiogenic drug yohimbine is a reinforcer in male and female rats. Neuropsychopharmacol. 50, 432–443 (2025). https://doi.org/10.1038/s41386-024-01985-1

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