Dopamine receptor antagonists block nerve growth factor-induced hyperactivity

The role of dopamine receptors in mediating nerve growth factor (NGF)-induced locomotor stimulation was investigated by examining the effects of selective dopamine D1 and D2 receptor antagonists on the motor hyperactivity induced by NGF. A single intracerebroventricular administration of NGF (5.1 microg) increased locomotor activity immediately after injection in normal adult rats. This hyperactivity was partly blocked by the dopamine D1 receptor antagonist SCH23390 (R-(+)-7-chloro-2,3,4,5-tetrahydro-3-methyl-1-phenyl-1H-3-benzazepine-8- ol) and by the dopamine D2 antagonist raclopride ((S)-3,5-dichloro-N-((1-ethyl-2-pyrrolidinyl)methyl)-2-hydroxy-6-methoxy benzamide). Effective doses of raclopride did not alter spontaneous levels of activity in control rats. These results suggest that stimulation of both subtypes of dopamine receptors is necessary for eliciting NGF-induced hyperactivity in the rat. The role of the dopamine D2 receptor in mediating the behavioral actions of NGF appears to be more important than that of the dopamine D1 receptor.