Inhibition of striatal acetylcholine release by endogenous serotonin.
We have examined the hypothesis that endogenous serotonin (5-HT) exerts an inhibitory influence on the release of acetylcholine (ACh) in striatum. Striatal slices were prepared from adult rats, preincubated with [3H]choline, superfused, and exposed to electrical field stimulation. The stimulation-induced overflow of tritium into the superfusate was used as a measure of ACh release. We observed that fluoxetine, an inhibitor of 5-HT uptake, reduced ACh overflow in slices prepared from caudal striatum, an area of high 5-HT concentration, but not in slices from rostral striatum, an area of low 5-HT concentration. Moreover, methysergide, a 5-HT antagonist, increased ACh efflux in caudal but not rostral striatum. Finally, direct activation of 5-HT receptors with the 5-HT agonist, quipazine, inhibited stimulation-induced ACh overflow in both rostral and caudal striatum. These results suggest that endogenous 5-HT normally is capable of inhibiting striatal ACh release, and that the extent of the modulation is related to the degree of serotonergic innervation. In addition, 5-HT receptors capable of modulating ACh release are present in 5-HT-poor rostral striatum, as well as in 5-HT-rich caudal striatum.
Jackson
D
D
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
Stachowiak
M K
MK
Bruno
J P
JP
Zigmond
M J
MJ
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000032:analysis / Q000378:metabolism*; D004298:Dopamine / Q000032:analysis; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000032:analysis / Q000502:physiology*
D012701:Serotonin; D000109:Acetylcholine; D004298:Dopamine