5-HT2 antagonists and minaprine block the 5-HT-induced inhibition of dopamine release from rat brain striatal slices.
5-Hydroxytryptamine (5-HT) inhibited the K+-induced [3H]dopamine [( 3H]DA) release from slices of rat striatum. Minaprine (3-(2-morpholinoethylamino)-4-methyl-6-phenylpyridazine) attenuated the inhibitory effect of 5-HT in a dose-dependent manner. 5-HT2 receptor antagonists, ketanserin and mianserin, prevented the effect of 5-HT as well as minaprine did. The inhibitory effect of 5-HT was not mimicked by a 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), and was not prevented by a 5-HT1A and 5-HT1B mixed receptor antagonist, propranolol. Minaprine was a potent inhibitor of the binding of [3H]ketanserin to binding sites in the striatum over the concentration range 10(-6)-10(-4) M. Lesion of the medial forebrain bundle with 6-hydroxydopamine (6-OHDA) significantly reduced the K+-induced [3H]DA release from the striatum and release was no longer inhibited by 5-HT. Lesioning, however, did not change significantly the [3H]ketanserin binding in the striatum. These results suggest that minaprine suppresses the inhibitory effect of 5-HT on DA release in the striatum via the inhibition of 5-HT binding at the 5-HT2 receptor on the nerve terminal of the DA-ergic neuron and, further, that the proportion of the 5-HT2 receptor site which is located on the nerve terminal of the DA-ergic neuron is small in the striatum.
Muramatsu
M
M
Research Center, Taisho Pharmaceutical Co. Ltd., Saitama, Japan.
Tamaki-Ohashi
J
J
Usuki
C
C
Araki
H
H
Chaki
S
S
Aihara
H
H
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D007650:Ketanserin / Q000378:metabolism; D008297:Male; D008474:Medial Forebrain Bundle / Q000187:drug effects / Q000378:metabolism; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D011724:Pyridazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology
D000928:Antidepressive Agents; D011724:Pyridazines; D012702:Serotonin Antagonists; D013764:Tetrahydronaphthalenes; C006149:minaprine; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D007650:Ketanserin; D004298:Dopamine