Presentation Details
| Determining How The Intranasal Chemesthetic Sensation of Cocaine Contributes to Addiction Maria F.Ramirez1, Abhishek Gour2, Sarah E.Sniffen1, Emma Watson1, Abhisheak Sharma2, Daniel W.Wesson1. 1Department of Pharmacology & Therapeutics and Department of Neuroscience, Florida Chemical Senses Institute, University of Florida College of Medicine, Gainesville, FL, USA.2Department of Pharmaceutics, University of Florida College of Pharmacy, Gainesville, FL, USA |
Abstract
Chemosensory perception powerfully influences motivated behaviors. Cocaine, a highly addictive psychostimulant, is primarily taken intranasally – a route of delivery associated with high abuse liability. Intranasal cocaine evokes a nasal sensory experience which likely influences the effects of drugs and possibility drug abuse, yet preclinical models relying on intravenous or intraperitoneal administration do not recapitulate the insufflation of cocaine. Understanding how intranasal cocaine and its nasal sensation impact brain and behavior are both major unknown voids in fully resolving the brain’s reward system and how chemosensation impacts drug abuse. Here we report the development of an in-dwelling microfluidic device, the nasal access port (NAP). When implanted upon the nasal bone, the NAP permits access to the nasal epithelium of freely behaving rodents to achieve intranasal delivery of drugs with precise control over volume and dosage. First, we validated that intranasal infusion of cocaine rapidly results in detectable levels of cocaine in the plasma and brain, as well as increases in dopamine levels in the reward system. Next, we found that cocaine-infused mice display hyperlocomotion within just minutes post-infusion. Additionally, we show mice extended effort to acquire cocaine intranasally by engaging in an intranasal drug self-administration paradigm in the absence of instrumental cues, except for the nasal sensation evoked by cocaine infusions into the nasal epithelium. Importantly, we observed a rapid sneeze reflex evoked upon delivery of intranasal cocaine, indicative of the sensory response induced by cocaine agonism. Together, this work begins to establish a pre-clinical paradigm to investigate the role of chemosensation in addiction and what mechanisms are at play.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.
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