Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum
| Autor: | Joseph P. Huston, L.A. Ruocco, Claudio Arra, Placido Illiano, A. Scorziello, A.G. Sadile, Angela Tino, C Treno, Maria Nieddu, Susanne Nikolaus, M.A. de Souza Silva, Cristina Pagano, Claudia Mattern, U.A. Gironi Carnevale, Gianpiero Boatto |
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| Přispěvatelé: | L. A., Ruocco, C., Treno, U. A., Gironi Carnevale, C., Arra, C., Mattern, J. P., Huston, M. A., de Souza Silva, S., Nikolau, Scorziello, Antonella, M., Nieddu, G., Boatto, P., Illiano, C., Pagano, A., Tino, A. G., Sadile, Ruocco, L. A., Treno, C., Gironi Carnevale, U. A., Arra, C., Mattern, C., Huston, J. P., de Souza Silva, M. A., Nikolaus, S., Scorziello, A., Nieddu, M., Boatto, G., Illiano, P., Pagano, C., Tino, A., Sadile, Adolfo |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
Male
medicine.medical_specialty Intranasal dopamine Dopamine Dopamine Agents Clinical Biochemistry Substantia nigra Striatum L-Aspartate Biochemistry Rats Sprague-Dawley Internal medicine medicine Animals Humans ADHD Attention Sexual Maturation Prefrontal cortex Administration Intranasal Dopamine transporter Dose-Response Relationship Drug Tyrosine hydroxylase biology Chemistry Organic Chemistry Working memory L-Glutamate NMDA receptor Rats Ventral tegmental area Disease Models Animal Endocrinology medicine.anatomical_structure nervous system Attention Deficit Disorder with Hyperactivity Anesthesia Ventral Striatum biology.protein medicine.drug |
| Zdroj: | Amino acids (Wien, Print) 46 (2014): 2105–2122. doi:10.1007/s00726-014-1753-8 info:cnr-pdr/source/autori:Ruocco, Lucia A.; Treno, Concetta; Gironi Carnevale, Ugo Antonello; Arra, Claudio; Mattern, Claudia M.; Huston, Joseph Patrick; De Souza Silva, Maria Angélica; Nikolaus, Susanne; Scorziello, Antonella; Nieddu, Maria; Boatto, Giampiero; Illiano, Placido; Pagano, Cristina; Tino, Angela; Sadile, Adolfo Gustavo/titolo:Prepuberal intranasal dopamine treatment in an animal model of ADHD ameliorates deficient spatial attention, working memory, amino acid transmitters and synaptic markers in prefrontal cortex, ventral and dorsal striatum/doi:10.1007%2Fs00726-014-1753-8/rivista:Amino acids (Wien, Print)/anno:2014/pagina_da:2105/pagina_a:2122/intervallo_pagine:2105–2122/volume:46 |
| DOI: | 10.1007/s00726-014-1753-8 |
| Popis: | Intranasal application of dopamine (IN-DA) has been shown to increase motor activity and to release DA in the ventral (VS) and dorsal striatum (DS) of rats. The aim of the present study was to assess the effects of IN-DA treatment on parameters of DA and excitatory amino acid (EEA) function in prepuberal rats of the Naples High Excitability line (NHE), an animal model for attention-deficit hyperactivity disorder and normal random-bred (NRB) controls. Methods: NHE and NRB rats were daily administered INDA (0.075, 0.15, 0.30 mg/kg) or vehicle for 15 days from postnatal day 28 to 42 and subsequently tested in the Làt maze and in the eight arm radial Olton maze. Soluble Powered by Editorial Manager® and ProduXion Manager® from Aries Systems Corporation and membrane-trapped L-Glutamate (L-Glu) and L-Aspartate (L-Asp) levels as well as NMDAR1 subunit protein levels were determined post mortem in IN-DA- and vehicletreated NHE and NRB rats in prefrontal cortex (PFc), DS and VS. Moreover DA transporter (DAT) protein and tyrosine hydroxylase (TH) levels were assessed in PFc, DS, VS and mesencephalon (MES) and in ventral tegmental area and substantia nigra, respectively. Results: In NHE rats, IN-DA (0.30mg/kg) decreased horizontal activity and increased non-selective attention relative to vehicle, whereas the lower dose (0.13 mg/kg) increased selective spatial attention. In NHE rats, basal levels of soluble EEAs were reduced in PFc and DS relative to NRB controls, while membrane-bound EEAs were elevated. Moreover, basal NMDAR1 subunit protein levels were increased in PFc, DS and VS relative to NRB controls. Also DAT protein levels were elevated in PFc, VS and MES relative to NRB controls. IN-DA led to a number of changes of EAA, NMDRR1 subunit protein, TH and DAT protein levels in PFc, DS, VS, MES and VTA, in both NHE and NRB rats with significant differences between strains. Conclusions: Our findings indicate that the NHE rat model of ADHD may be characterized by (1) prefrontal and striatal DAT hyperfunction, indicative of DA hyperactivty, and (2) prefrontal and striatal NMDA receptor hyperfunction indicative of net EAA hyperactivty. IN-DA had ameliorative effects on activity level, attention, and working memory, which are likely to be associated with DA action at inhibitory D2 autoreceptors, leading to a reduction of striatal DA hyperactivity and, possibly, DA action striatal EAA levels, leading to a reduction of striatal EAA hyperfunction (with persistence of prefrontal EAA hyperfunction). Previous studies on IN-DA treatment in rodents have indicated antidepressant, anxiolytic and anti-parkinsonian effects in relation to enhanced central dopaminergic activity. Our present results strengthen the prospects of potential therapeutic applications of intranasal application of dopamine by indicating also an enhancement of selective attention and working memory in a deficit model. |
| Databáze: | OpenAIRE |
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