Journal of Neuroscience, Vol 14, 1262-1270, Copyright © 1994 by Society for Neuroscience
Brain-derived neurotrophic factor and neurotrophin-3 activate striatal dopamine and serotonin metabolism and related behaviors: interactions with amphetamine
MT Martin-Iverson, KG Todd and CA Altar
Department of Psychiatry, Walter Mackenzie Health Sciences Centre, University of Alberta, Edmonton, Canada.
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.
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