Nafadotride administration increases D1 and D1/D2 dopamine receptor mediated behaviors.
The administration of nafadotride, given at doses known to block the D3 dopamine receptors (0.75, 1.5, 3 mg/kg i.p.) increased locomotor activity both in naive and habituated rats and counteracted the hypothermia but not the hypomotility induced by a low dose of the putative D3 dopamine agonist (+/-)-7-hydroxy-2-(di-N-propylamino)-tetralin (7-OH-DPAT; 0.04 mg/kg). Nafadotride did not antagonize either the motor effects induced by different doses of the D2 agonist quinpirole (0.05 and 0.3 mg/kg) or the hypermotility induced by 7-OH-DPAT given at a dose (0.32 mg/kg) stimulating D2 dopamine receptors. The same nafadotride doses potentiated the grooming behavior induced by the D1 dopamine agonist SKF 38393 (10 mg/kg i.p.) as well as the stereotyped response to the D1/D2 agonist apomorphine (0.5 mg/kg s.c.). Stereotyped behavior was also observed in rats concomitantly treated with nafadotride and the D2 agonist quinpirole. As the activation of D1 dopamine receptors plays an important role in the occurrence of stereotypies, the results suggest that the blockade of D3 receptors by nafadotride could have favored D1/D2 dopamine receptor-mediated behaviors by potentiating D1 receptor function.
Dall'Olio
R
R
Department of Pharmacology, University of Bologna, Via Irnerio 48, I 40126, Bologna, Italy. dallolio@biocfarm.unibo.it
Gaggi
R
R
Voltattorni
M
M
Tanda
O
O
Gandolfi
O
O
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000494:pharmacology; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001522:Behavior, Animal / Q000187:drug effects*; D001831:Body Temperature / Q000187:drug effects; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009281:Naphthalenes / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D019257:Quinpirole / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000037:antagonists & inhibitors*; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D050637:Receptors, Dopamine D3; D013239:Stereotyped Behavior / Q000187:drug effects; D013268:Stimulation, Chemical; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; C493595:Drd3 protein, rat; D009281:Naphthalenes; D011759:Pyrrolidines; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; C097285:nafadotride; D001058:Apomorphine; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine