Original Article

Neuropsychopharmacology (2014) 39, 2131–2141; doi:10.1038/npp.2014.61; published online 23 April 2014

Intranasal Delivery of a Peptide with Antidepressant-Like Effect

Virginia Brown1 and Fang Liu1,2

  1. 1Department of Neuroscience, Centre for Addiction and Mental Health, Toronto, ON, Canada
  2. 2Department of Psychiatry, University of Toronto, Toronto, ON, Canada

Correspondence: Dr F Liu, Department of Neuroscience, Centre for Addiction and Mental Health, 250 College Street, Toronto, ON M5T 1R8, Canada, Tel: +1 416 979 4659, Fax: +1 416 979 4663, E-mail: f.liu.a@utoronto.ca

Received 21 January 2014; Revised 25 February 2014; Accepted 10 March 2014
Accepted article preview online 17 March 2014; Advance online publication 23 April 2014

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Abstract

A critical issue in drug development is developing effective, noninvasive delivery routes to the central nervous system (CNS). Major depressive disorder (MDD) is an illness associated with significant morbidity. Even with multiple antidepressant trials, 10–15% of patients continue to experience persistent depressive symptoms. We previously developed an interfering peptide that has antidepressant-like effects in rats when injected directly into the brain. To be clinically viable, it must demonstrate efficacy via a noninvasive administration route. We report here that the interfering peptide designed to disrupt the interaction between the D1 and D2 dopamine receptors can be delivered to relevant brain areas using the Pressurized Olfactory Device (POD), a novel intranasal delivery system developed by Impel NeuroPharma. We validate this delivery method by demonstrating that, at doses greater than or equal to1.67nmol/g, the D1–D2 interfering peptide has a significant antidepressant-like effect comparable to that of imipramine in the forced swimming test (FST), a common test for antidepressant efficacy. The antidepressant-like effect of the interfering peptide can be detected for 2h after intranasal administration. Furthermore, we show that the interfering peptide disrupts the D1–D2 interaction and it can be detected in the prefrontal cortex after intranasal administration. This study provides strong preclinical support for intranasal administration of the D1–D2 interfering peptide as a new treatment option for patients suffering from MDD.

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