RT Journal Article
SR Electronic
T1 [3H]dopamine and [3H]serotonin release in vitro induced by electrical stimulation in A9 and A10 dopamine regions of rat brain: characterization and responsiveness to cocaine.
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 379
OP 389
VO 267
IS 1
A1 N H Chen
A1 M E Reith
YR 1993
UL http://jpet.aspetjournals.org/content/267/1/379.abstract
AB The present study investigated [3H]dopamine (DA) and [3H]5-hydroxytryptamine (5-HT) release evoked by electrical stimulation in superfused ventral mesencephalon (VM) slices containing A9 and A10 DA neurons. Electrically induced [3H]DA release from VM was, at least, of two origins: one was from DA somatodendrites, regulated by DA autoreceptors, and increased by DA uptake blockers; another was from 5-HT terminals, modulated by 5-HT autoreceptors, and could be minimized by the copresence of fluoxetine during the labeling of the slices. Release of both origins was Ca(++)-dependent and tetrodotoxin-sensitive. Cocaine (10 and 100 microM) modestly increased electrically induced [3H]DA release from DA somatodendrites and concentration-dependently inhibited that from 5-HT terminals. Electrically induced [3H]5-HT release from VM was exclusively from 5-HT terminals, dependent on Ca++, partly blocked by tetrodotoxin, increased by 5-HT uptake blockers and regulated by 5-HT autoreceptors. The autoregulation of [3H]5-HT release partly counteracted the stimulatory effect of cocaine (10 microM) on [3H]5-HT release. Inhibition of 5-HT uptake by cocaine reduced the effectiveness of 5-methoxytryptamine to suppress electrically induced [3H]5-HT release. No evidence was found to support the notion that postsynaptic 5-HT receptors modulate somatodendritic DA release. 5-HT facilitated spontaneous [3H]DA release from VM via a 5-HT/DA transporter-dependent exchange process and inhibited electrically induced [3H]DA release from 5-HT terminals via a 5-HT autoreceptor-mediated mechanism. The dual effects of cocaine on electrically induced [3H]DA release from VM may be attributed to the complex 5-HT/DA and 5-HT autoreceptor/cocaine interactions as well as the relative densities of 5-HT/DA transporters in this region, indicating a possible involvement of the 5-HT system in cocaine's behavioral effects.