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| Poster #286 Determining the contribution of intranasal chemesthetic sensation on addiction. |
| Maria F. Ramirez1, Abhishek Gour2, Emma K Watson1, Abhisheak Sharma2, Daniel Wesson1 1Department of Pharmacology & Therapeutics, Department of Neuroscience, and Florida Chemical Senses Institute , College of Medicine, Gainesville, FL, United States 2Department of Pharmaceutics, College of Pharmacy, Gainesville, FL, United States |
Chemosensory cues are instrumental in guiding motivated behaviors and affective states. Not surprisingly, many drugs of abuse are chemosensory rich. Cocaine, in addition to its psychostimulant effects on the dopaminergic system, also evokes nasal sensation upon inhalation. The mechanisms underlying sensation of cocaine and how it may impact cocaine abuse liability are both unknown. Here we report the development of a reliable surgical implant which permits access to the nasal epithelium of freely behaving mice for intranasal delivery of cocaine with precise control over volume and therefore dosage of drug. First, we validated that intranasal infusion of cocaine rapidly results in detectable levels of drug in the plasma and brain. Next, utilizing canonical behavioral assays of drug response, we found that cocaine-infused mice display hyperlocomotion within minutes post-infusion and exhibit instrumental responding for cocaine. Specifically, mice extended effort to acquire cocaine intranasally when engaged in an intranasal drug self-administration paradigm, with some mice displaying strong responding to nose poke in a cocaine-associated port, in the absence of any other sensory cues. Furthermore, we observed a sneeze response and facial-grooming behavior evoked rapidly upon delivery of intranasal cocaine, suggestive of the sensory response induced by cocaine agonism. Currently, we are investigating the sneeze reflex induced by intranasal drug delivery in combination with simultaneous monitoring of brain dopamine dynamics to unravel the role of intranasal chemesthetic sensation in directing drug seeking. Together, this work begins to establish a pre-clinical paradigm to investigate the role of chemosensation in the perceptional qualities of drugs of abuse. |