Effects of intranasally applied dopamine on behavioral asymmetries in rats with unilateral 6-hydroxydopamine lesions of the nigro-striatal tract.
Due to its lipophobic properties, dopamine is unable to cross the blood-brain barrier following systemic application. However, recently it has been demonstrated that, when applied directly via the nasal passages in the rat, dopamine exerts neurochemical and behavioural action, including increases of dopamine in striatal subregions, antidepressive-like action, and increased behavioral activity. These effects could potentially be mediated by exogenous dopamine acting as a direct agonist at postsynaptic dopamine receptors. However, it is also possible that intranasally applied dopamine acts indirectly via the modulation of the activity of dopaminergic cell bodies. To approach this question, the present study used rats with unilateral 6-hydroxydopamine (6-OHDA) lesions of the nigrostriatal tract, as these lesions lead to pharmacologically stimulated behavioural asymmetries which are specific for direct and indirect dopamine agonists. We found that 7 days of repeated treatment with intranasal dopamine induced a sensitization of the turning response to amphetamine, but not to apomorphine. Furthermore, intranasal dopamine dose-dependently increased the use of the forepaw ipsilateral to the 6-OHDA-lesioned side of the brain. These results suggest that intranasally administered dopamine acts via an indirect mechanism of action, putatively by increasing the release of endogenous dopamine in the brain.
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Institute of Physiological Psychology and Center for Biological and Medical Research, University of Düsseldorf, Universitätsstrasse 1, 40225 Düsseldorf, Germany. Martin.Pum@uni-duesseldorf.de
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Harooni
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De Souza Silva
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Li
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Huston
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D000281:Administration, Intranasal; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects / Q000293:injuries* / Q000378:metabolism; D004298:Dopamine / Q000008:administration & dosage* / Q000378:metabolism; D015259:Dopamine Agents / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005552:Forelimb; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D009638:Norepinephrine / Q000378:metabolism; D009714:Nucleus Accumbens / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity; D017397:Prefrontal Cortex / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000293:injuries*
D015259:Dopamine Agents; D012701:Serotonin; D016627:Oxidopamine; D004298:Dopamine; D009638:Norepinephrine