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 t egmental area and provides trophic support for these neurons in vitro. To study the effects of BDNF on the nigrostriatal dopaminergic system in. vivo, we administered a single, unilateral injection of BDNF into the medial SNpc of rats and evaluated rotational behavior, striatal l evels of dopamine and metabolites, and number of dopaminergic neurons in the SNpc. We found that a single injection of 2 or 3 mu g Of BDNF, but not of vehicle, caused a persistent increase in the net number of amphetamine-induced rotations/min contraversive to the site of injecti on. The pattern of rotation is consistent with increased activity of t he nigrostriatal dopaminergic system on the side of injection. The amp hetamine-induced contraversive rotation could be blocked by administra tion of the dopaminergic antagonist haloperidol. Apomorphine, a direct -acting dopaminergic agonist, did not induce rotation. Levels of dopam ine in the striatum and number of dopaminergic neurons in the SNpc wer e similar in BDNF- and vehicle-treated animals. The increase in contra versive rotations persisted for up to 12 months after a single injecti on of BDNF. (C) 1994 Academic Press, Inc.