BRAIN-DERIVED NEUROTROPHIC FACTOR AND NEUROTROPHIN-3 ACTIVATE STRIATAL DOPAMINE AND SEROTONIN METABOLISM AND RELATED BEHAVIORS - INTERACTIONS WITH AMPHETAMINE

To investigate behavioral and neurochemical effects of neurotrophic fa ctors in vivo, rats received continuous 14 d infusions of either brain -derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), or vehicle unilaterally into the substantia nigra. BDNF and NT-3 decreased body weights, an effect that was sustained over the infusion period. BDNF e levated daytime and nocturnal locomotion compared with infusions of ve hicle or NT-3. At 2 weeks, a systemic injection of amphetamine(1.5 mg/ kg, s.c.) increased the frequencies and durations of rotations contrav ersive to the side of BDNF and NT-3 infusions. Both factors attenuated amphetamine-induced locomotion without affecting amphetamine-induced stereotyped behaviors such as sniffing, head movements, and snout cont act with cage surfaces. Only BDNF induced backward walking, and this r esponse was augmented by amphetamine. BDNF, but not NT-3, increased do pamine turnover in the striatum ipsilateral to the infusion relative t o the contralateral striatum. Both trophic factors decreased dopamine turnover in the infused substantia nigra relative to the contralateral hemisphere and increased 5-HT turnover in the striatum of both sides. Contraversive rotations were positively correlated with dopamine cont ent decreases and 5-HT turnover increases in the striatum ipsilateral to the infused substantia nigra. Backward walking was positively corre lated with increased dopamine and 5-HT turnover in the striatum of the infused hemisphere. Supranigral infusions of BDNF and NT-3 alter circ adian rhythms, spontaneous motor activity, body weights, and amphetami ne-induced behaviors including locomotion and contraversive rotations. These behavioral effects of the neurotrophins are consistent with a c oncomitant activation of dopamine and 5-HT systems in vivo.