Nafadotride administration increases D1 and D1/D2 dopamine receptor mediated behaviors

The administration of nafadotride, given at doses known to block the D-3 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 D-3 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 D-2 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 D-2 dopamine receptors. The same nafadotride doses potentiated the grooming behavior induced by the D-1 dopamine agonist SKF 38393 (10 mg/kg i.p.) as well as the stereotyped response to the D-1/D-2 agonist apomorphine (0.5 mg/kg s.c.). Stereotyped behavior was also observed in rats concomitantly treated with nafadotride and the D-2 agonist quinpirole. As the activation of D-1 dopamine receptors plays an important role in the occurrence of stereotypies, the results suggest that the blockade of D-3 receptors by nafadotride could have favored D-1/D-2 dopamine receptor-mediated behaviors by potentiating D-1 receptor function. (C) 2002 Lippincott Williams Wilkins.