Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: Interactions with amphetamine

Abstract

To investigate behavioral and neurochemical effects of neurotrophic factors 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 elevated daytime and nocturnal locomotion compared with infusions of vehicle or NT-3. At 2 weeks, a systemic injection of amphetamine (1.5 mg/kg, s.c.) increased the frequencies and durations of rotations contraversive 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 contact with cage surfaces. Only BDNF induced backward walking, and this response was augmented by amphetamine. BDNF, but not NT-3, increased dopamine turnover in the striatum ipsilateral to the infusion relative to 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 content decreases and 5-HT turnover increases in the striatum ipsilateral to the infused substantia nigra. Backward walking was positively correlated with increased dopamine and 5-HT turnover in the striatum of the infused hemisphere. Supranigral infusions of BDNF and NT-3 alter circadian rhythms, spontaneous motor activity, body weights, and amphetamine-induced behaviors including locomotion and contraversive rotations. These behavioral effects of the neurotrophins are consistent with a concomitant activation of dopamine and 5-HT systems in vivo.