Intranasal Administration of the Dopaminergic Agonists l‐DOPA, Amphetamine, and Cocaine Increases Dopamine Activity in the Neostriatum: A Microdialysis Study in the Rat

Abstract

The effectiveness of intranasal drug administration to stimulate central neuronal systems is well known from drug addiction and has also been considered as an alternative pharmacokinetic approach to treat brain disorders such as Parkinson's disease. In the present study, the possible neurochemical effects of intranasal administration of the psychostimulants cocaine and amphetamine and of the antiparkinsonian drug l‐DOPA were analyzed. By using in vivo microdialysis in the urethane‐anesthetized rat, it was found that unilateral intranasal administration of either of the psychostimulants led to huge and rapid increases of extracellular dopamine levels in the neostriatum followed by decreases of its metabolites dihydroxyphenylacetic acid and homovanillic acid. Furthermore, intranasal administration of l‐DOPA, but not of the saline vehicle, also led to increased extracellular levels of neostriatal dopamine and to increases of its metabolites. Because the effect of intranasal l‐DOPA on neostriatal dopamine was observed only ipsilaterally but not contralaterally to the side of intranasal drug administration, it can be hypothesized that l‐DOPA was not effective via passage through the circulation but may have acted through a neuronal or an extraneuronal route. These data provide neurochemical evidence that the intranasal route may not only be efficient in drug abuse, but may also be useful to target the brain therapeutically, as in the case of neurodegenerative brain disorders.

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

“…As postulated [81] , behavioral and neurochemical effects of labelled DA applied either by intra-nasal or intravenous route should be compared to validate the uptake and distribution of labelled DA in the brain in future studies. Nevertheless, the rapid behavioral effects in the present study along with quick neurochemical effects in our previous ones [10][11][12] , strongly suggest a fast transport mechanism into the brain. Thus, the intra-nasal application procedure may represent a valuable alternative for targeting the brain with exogenous DA, resulting in rapid neurochemical and behavioral effects.…”

“…Previously, we demonstrated that L -DOPA readily enters the brain upon intra-nasal application, leading to increases in extracellular levels of DA in neostriatal regions [10,11] . Additionally, recently, we found evidence that DA, administered intra-nasally in the rat, can also enter the brain, leading to an immediate pronounced increase in extracellular DA levels in striatal subregions [12] .…”

“…We have demonstrated that intra-nasal administration of L -DOPA ( L -3,4-dioxyphenylalanine), the mainstay of therapies in dopamine (DA) deficiencies, such as Parkinson's disease, led to an increase in extracellular levels of DA and its metabolites in neostriatal regions [10,11] . Administration of DA via oral or parenteral delivery is limited due to poor absorption, rapid metabolism in the periphery and the inability of DA to cross the bloodbrain barrier, which rules out its application by the conventional oral, intravenous, intramuscular or subcutaneous routes.…”

Role of medial prefrontal, entorhinal, and occipital 5-HT in cocaine-induced place preference and hyperlocomotion: evidence for multiple dissociations

“…The ventral striatum, dorsal striatum, medial prefrontal cortex, hippocampus, entorhinal cortex, and occipital cortex were dissected, homogenized, centrifuged, filtered, and stored at −80°C until analysis for dopamine and serotonin content (De Souza Silva et al 1997). Samples, containing 400 pg deoxyepinephrine as an internal standard, were analyzed by high-performance liquid chromatography with electrochemical detection.…”

Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles

“…Instead of the oral and intravenous route, the intranasal drug administration is receiving great consideration as a promising pharmacokinetic approach for the PD treatment. To this regard, de Souza Silva and colleagues, for the first time, showed by in vivo microdialysis that intranasal administration of dopaminergic drugs such as the psychostimulants cocaine and amphetamine or the antiparkinsonian drug L-Dopa can increase extracellular DA levels in the striatum [9,10]. These interesting results have encouraged further to pursuit of this approach.…”