Teddy Talbot1,2, Claudia Mattern3,4, Maria Angelica de Souza Silva5, Marcus Lira Brandão1,2. 1. 1 Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil. 2. 2 Instituto de Neurociências e Comportamento, Avenida do Café, Ribeirão Preto, SP, Brazil. 3. 4 Oceanographic Center, Nova Southeastern University, Fort Lauderdale, FL, USA. 4. 5 M et P Pharma AG, Emmetten, Switzerland. 5. 3 Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University, Düsseldorf, Germany.
Abstract
BACKGROUND: Although substantial evidence suggests that dopamine (DA) enhances conditioned fear responses, few studies have examined the role of DA in unconditioned fear states. Whereas DA does not cross the blood-brain barrier, intranasally-applied dopamine reaches the brain directly via the nose-brain pathways in rodents, providing an alternative means of targeting DA receptors. Intranasal dopamine (IN-DA) has been demonstrated to bind to DA transporters and to increase extracellular DA in the striatum as well as having memory-promoting effects in rats. The purpose of this study was to examine the influence of IN-DA in three tests of fear/anxiety. METHODS: The three doses of DA hydrochloride (0.03, 0.3, or 1 mg/kg) were applied in a viscous castor oil gel in a volume of 5 µl to each of both nostrils of adult Wistar rats prior to testing of (a) escape from a bright light, using a two-chamber procedure, (b) restraint-induced 22 kHz ultrasound vocalizations (USVs), and (c) exploratory behavior in the elevated plus-maze (EPM). RESULTS: IN-DA dose-dependently reduced escape from bright light and the number of USV responses to restraint. It had no influence on the exploratory behavior in the EPM. CONCLUSIONS: IN-DA application reduced escape behavior in two tests of unconditioned fear (escape from bright light and USV response to immobilization). These findings may be interpreted in light of the known antidepressant action of IN-DA and DA reuptake blockers. The results also confirm the promise of the nasal route as an alternative means for targeting the brain's dopaminergic receptors with DA.
BACKGROUND: Although substantial evidence suggests that dopamine (DA) enhances conditioned fear responses, few studies have examined the role of DA in unconditioned fear states. Whereas DA does not cross the blood-brain barrier, intranasally-applied dopamine reaches the brain directly via the nose-brain pathways in rodents, providing an alternative means of targeting DA receptors. Intranasal dopamine (IN-DA) has been demonstrated to bind to DA transporters and to increase extracellular DA in the striatum as well as having memory-promoting effects in rats. The purpose of this study was to examine the influence of IN-DA in three tests of fear/anxiety. METHODS: The three doses of DA hydrochloride (0.03, 0.3, or 1 mg/kg) were applied in a viscous castor oil gel in a volume of 5 µl to each of both nostrils of adult Wistar rats prior to testing of (a) escape from a bright light, using a two-chamber procedure, (b) restraint-induced 22 kHz ultrasound vocalizations (USVs), and (c) exploratory behavior in the elevated plus-maze (EPM). RESULTS:IN-DA dose-dependently reduced escape from bright light and the number of USV responses to restraint. It had no influence on the exploratory behavior in the EPM. CONCLUSIONS:IN-DA application reduced escape behavior in two tests of unconditioned fear (escape from bright light and USV response to immobilization). These findings may be interpreted in light of the known antidepressant action of IN-DA and DA reuptake blockers. The results also confirm the promise of the nasal route as an alternative means for targeting the brain's dopaminergic receptors with DA.
Authors: J Daniel Obray; Christina A Small; Emily K Baldwin; Eun Young Jang; Jin Gyeom Lee; Chae Ha Yang; Jordan T Yorgason; Scott C Steffensen Journal: Front Cell Neurosci Date: 2022-07-12 Impact factor: 6.147