A single intramesencephalic injection of brain-derived neurotrophic factor induces persistent rotational asymmetry in rats.

Brain-derived neurotrophic factor (BDNF) is expressed in dopaminergic neurons of the substantia nigra pars compacta (SNpc) and the ventral tegmental area and provides trophic support for these neurons in vitro. To study the effects of BDNF on the nigrostrital dopaminergic system in vivo, we administered a single, unilateral injection of BDNF into the medial SNpc of rats and evaluated rotational behavior, striatal levels of dopamine and metabolites, and number of dopaminergic neurons in the SNpc. We found that a single injection of 2 or 3 micrograms of BDNF, but not of vehicle, caused a persistent increase in the net number of amphetamine-induced rotations/min contraversive to the site of injection. The pattern of rotation is consistent with increased activity of the nigrostriatal dopaminergic system on the side of injection. The amphetamine-induced contraversive rotation could be blocked by administration of the dopaminergic antagonist haloperidol. Apomorphine, a direct-acting dopaminergic agonist, did not induce rotation. Levels of dopamine in the striatum and number of dopaminergic neurons in the SNpc were similar in BDNF- and vehicle-treated animals. The increase in contraversive rotations persisted for up to 12 months after a single injection of BDNF.