title: Intranasal administration of dopamine attenuates unconditioned fear in that it reduces restraint-induced ultrasound vocalizations and escape from bright light.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.affiliation: 1 Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil.|2 Instituto de Neurociências e Comportamento, Avenida do Café, Ribeirão Preto, SP, Brazil.
authors.forename: Teddy
authors.initials: T
authors.lastname: Talbot
authors.affiliation: 4 Oceanographic Center, Nova Southeastern University, Fort Lauderdale, FL, USA.|5 M et P Pharma AG, Emmetten, Switzerland.
authors.forename: Claudia
authors.initials: C
authors.lastname: Mattern
authors.affiliation: 3 Center for Behavioral Neuroscience, Institute of Experimental Psychology, Heinrich-Heine University, Düsseldorf, Germany.
authors.forename: Maria Angelica
authors.initials: MA
authors.lastname: de Souza Silva
authors.affiliation: 1 Laboratório de Neuropsicofarmacologia, FFCLRP, Universidade de São Paulo, Campus USP, Ribeirão Preto, SP, Brazil.|2 Instituto de Neurociências e Comportamento, Avenida do Café, Ribeirão Preto, SP, Brazil.
authors.forename: Marcus Lira
authors.initials: ML
authors.lastname: Brandão
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001812:Blood-Brain Barrier / Q000378:metabolism; D003214:Conditioning, Classical / Q000187:drug effects*; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000494:pharmacology*; D005239:Fear / Q000187:drug effects* / Q000502:physiology; D008027:Light; D008568:Memory; D009297:Nasal Mucosa / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism; D012149:Restraint, Physical / Q000502:physiology*
chemical_list: D017448:Receptors, Dopamine D2; D004298:Dopamine
keywords: Intranasal dopamine; elevated plus-maze; escape from bright light; ultrasonic vocalization