V. Hillegaart et al., A9 and A10 dopamine nuclei as a site of action for effects of 8-OH-DPAT onlocomotion in the rat, PHARM BIO B, 67(1), 2000, pp. 55-63
The 5-hydroxytryptamine (5-HT) 5-HT1A receptor agonist 8-hydroxy-2-(di-n-pr
opylamino)tetralin (8-OH-DPAT) was applied locally (0-5 mug bilaterally) in
to either the substantia nigra (A9) or the ventral tegmental area (A10) of
adult male Wistar rats, and 10 min later spontaneous motor activity was obs
erved in an open field (approximate to0.5 m(2)) for 30 min. The rate of dop
amine synthesis was estimated in neostriatal areas, the amygdala, and the p
refrontal cortex, by measuring the accumulation of DOPA, following inhibiti
on of cerebral decarboxylase by means of 3-hydroxybenzylhydrazine (NSD-1015
). The A10 application of 8-OH-DPAT resulted in an increase in all aspects
of spontaneous motor activity in the open field. A9 application of 8-OH-DPA
T produced a stereotyped forward locomotion, characterized by a modest decr
ease in total horizontal activity, almost complete inhibition of rearing ac
tivity, and an increase in proportion-forward locomotion along the perimete
r of the open-field arena. The injection of 8-OH-DPAT into the A9 was accom
panied by an increased neostriatal DA rate of synthesis, whereas the A10 in
jection was followed by a decreased DA rate of synthesis in the amygdala an
d in the prefrontal cortex. It is concluded that mesencephalic dopaminergic
mechanisms are involved in the stereotyped forward locomotion characterist
ically seen after systemic administration of the 5-HT1A receptor agonist 8-
OH-DPAT. (C) 2000 Elsevier Science Inc. All rights reserved.