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Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice

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Abstract

Rationale

Buprenorphine (BPN) has been shown to rapidly improve mood in treatment-resistant depressed patients in small clinical studies. However, BPN’s effects in preclinical tests for mood and antidepressant efficacy are largely unexplored.

Objective

The current study examined the effects of BPN in the forced swim test (FST) and novelty-induced hypophagia (NIH) test as measures of antidepressant and anxiolytic-like effects in C57BL/6 J mice. Microdialysis was used to measure whether BPN engaged kappa-opioid receptor (KORs) in the nucleus accumbens shell (NAcSh) at a behaviorally active dose (0.25 mg/kg).

Methods

BPN was tested in the FST at both 30 min and 24 h post-administration. Also measured in the FST at 24 h post-administration were the KOR antagonist norbinaltorphimine (nor-BNI), the MOR agonist morphine and the reference antidepressant desipramine. The anxiolytic effects of BPN were examined in the NIH test 24 h after treatment. The effects of acute injection of BPN and the KOR agonist U50,488 were measured on extracellular dopamine (DA) levels in the NAcSh.

Results

BPN produced significant reductions in FST immobility without changing locomotor activity and reduced approach latencies in the novel environment of the NIH test when tested 24 h after treatment. Repeated daily BPN injections for 6 days did not produce tolerance to these behavioral effects. nor-BNI produced a similar antidepressant-like response in the FST 24 h post-injection but morphine and desipramine were ineffective. BPN (0.25 mg/kg) did not alter DA levels when given alone but prevented the KOR agonist U50,488 from reducing DA levels.

Conclusions

Acute and subchronic treatment with BPN produced antidepressant and anxiolytic-like responses in mice at doses that engage KORs. These studies support the clinical evidence that BPN may be a novel rapid-acting antidepressant medication and provides rodent models for investigating associated neurochemical mechanisms.

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Acknowledgments

This research was supported by USPHS grants R01 MH92412 and T32 MH14654.

Conflict of interest

IL was a consultant for Alkermes. EF, KM, and SAR have no conflict to disclose.

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Authors and Affiliations

  1. Department of Psychiatry, University of Pennsylvania, 125 South 31st Street, Room 2204, Philadelphia, PA, 19104-3403, USA

    Edgardo Falcon, Kaitlyn Maier, Shivon A. Robinson, Tiffany E. Hill-Smith & Irwin Lucki

  2. Department of Pharmacology, University of Pennsylvania, Philadelphia, PA, 19104, USA

    Kaitlyn Maier & Irwin Lucki

Authors
  1. Edgardo Falcon
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  2. Kaitlyn Maier
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  3. Shivon A. Robinson
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  4. Tiffany E. Hill-Smith
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  5. Irwin Lucki
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Correspondence to Irwin Lucki.

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Falcon, E., Maier, K., Robinson, S.A. et al. Effects of buprenorphine on behavioral tests for antidepressant and anxiolytic drugs in mice. Psychopharmacology 232, 907–915 (2015). https://doi.org/10.1007/s00213-014-3723-y

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  • DOI: https://doi.org/10.1007/s00213-014-3723-y

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