Behavioral Actions of Intranasal Application of Dopamine: Effects on Forced Swimming, Elevated Plus-Maze and Open Field Parameters

Abstract

Background: Recently, we found evidence that intra-nasally administered dopamine (DA), can enter the brain, leading to an immediate increase in extracellular DA levels in striatal subregions. This offers a potential alternative approach to target the brain with exogenous DA, which otherwise cannot cross the blood-brain barrier. Here, we examined whether intra-nasally applied DA also exerts behavioral activity on mesocortical and nigrostriatal dopaminergic functions. Method: Male Wistar rats (3–4 months) were tested for potential behavioral effects of intra-nasally applied DA (0.03, 0.3 or 3.0 mg/kg) in the forced swimming test (FST) for antidepressant-like activity, elevated plus-maze for anxiety-related behavior, and on motor activity in a novel and familiar environment. Results: Intra-nasally administered dopamine in a dose of 0.3 mg/kg exerted antidepressant-like activity in the FST, but had neither anxiolytic-like nor anxiogenic-like effects in the elevated plus-maze. Furthermore, intra-nasal dopamine stimulated locomotor activity in a familiar, but not novel, open field. Conclusions: These results support the view that intra-nasally applied DA can act on the central nervous system by entering the brain via the nose-brain pathway, making this kind of application procedure a promising alternative for targeting the brain, and thus treating disorders involving mesocortical and/or nigrostriatal dopaminergic disturbances.

A sphingolipid mechanism for behavioral extinction

“…Dopaminergic dysfunctions are recognized as one mechanisms of depression (Chaudhury et al 2013). DA is a potentially antidepressant agent (Willner 1997;Willner et al 2005;Buddenberg et al 2008). DA-HCl (Sigma, St Louis, MO, USA; 0.3 mg/kg) was suspended in a vehicle gel (M et P Pharma AG, Emmetten, Switzerland).…”

“…reduce relearning during extinction, as shown in humans (Schwabe and Wolf 2011). Given the known antidepressant effects of DA agonists (Willner 1997;Willner et al 2005) and of intranasal DA (Buddenberg et al 2008), DA (i.n.) was expected to reduce EID-related behaviors, but decrease resistance to extinction (enhance re-learning) given its memory promoting action (Trossbach et al 2014).…”

Influence of intranasal administration of dopamine on realization of cognitive processes and locomotor activity of rats during stress

“…Першочерговою терапією для пацієнтів з ADHD вважається застосування D-амфетаміну та метилфенідату, які значно покращують основні симптоми, але мають негативні наслідки [6,7,13]. Існують експериментальні свідчення того, що інтраназальна аплікація речовин може бути шляхом до мішеней у центральну нервову систему [8,11,15,23]. Однією з альтернатив постачання ДА у центральні структури мозку в обхід ГЕБ може бути інтраназальне його введення [9,10].…”

Intranasal Dopamine Reduces In Vivo [123I]FP-CIT Binding to Striatal Dopamine Transporter: Correlation with Behavioral Changes and Evidence for Pavlovian Conditioned Dopamine Response

“…Application of IN-DA into the nostrils of anesthetized rats was also shown to increase extracellular DA in the dorsal and ventral striatum for at least 2 h by as much as 250% (de Souza Silva et al, 2008 ). In the freely moving rat, IN-DA influenced motor activity and exerted antidepressant-like effects (Buddenberg et al, 2008 ). In aged rats, IN-DA was found to restore deficient object-place memory (Trossbach et al, 2014 ).…”