INTRAVENTRICULAR-INJECTION OF NGF, BUT NOT BDNF, INDUCES RAPID MOTOR ACTIVATION THAT IS INHIBITED BY NICOTINIC RECEPTOR ANTAGONISTS

The acute and subacute effects of intracerebroventricularly (ICV) admi nistered nerve growth factor (NGF) or brain-derived neurotrophic facto r (BDNF) on locomotor activity were evaluated in awake adult rats. Imm ediately after ICV injection through an implanted cannula, locomotor a ctivity was measured by a computerized system using infrared photocell s, which allowed us to record locomotion, motility, and rearing simult aneously. A single dose of 5 mu g mouse beta-NGF produced significant increases in horizontal ambulatory components of locomotor activity (l ocomotion and motility), but not vertical movement (rearing) 30-45 min after ICV administration. These increases lasted for at least 3-4 h. Systemic injection of 2.0 mg/kg mecamylamine, a central nicotinic rece ptor antagonist, inhibited the hyperactivity induced by NGF. Systemic injection of 0.5 mg/kg scopolamine, a muscarinic receptor antagonist, did not interfere with the NGF effects. Thus, while scopolamine induce d marked increases in all three measures of behavior in both NGF and c ytochrome-c-treated animals, locomotion and motility remained signific antly higher in the NGF group. Immunohistochemistry demonstrated that NGF diffused readily from the ventricular space into brain parenchyma on the injected side and could be visualized 1 h after ICV injection. These results suggest that ICV administration of NGF increases locomot or activity by inducing acetylcholine release, and that nicotinic rece ptors are involved in the hyperactivity induced by NGF. ICV administra tion of 5 mu g recombinant human BDNF had no significant effect on loc omotor activity during the 0- to 4-h period after ICV injection. Howev er, it produced significant decreases in locomotion, motility, and rea ring 24-26 h later. Hence ICV administration of BDNF has entirely diff erent effects on animal behavior from those evoked by NGF. While NGF e licits increases in ambulatory behavior within hours, BDNF causes dela yed decreases in ambulatory behavior.