Characterization of endogenous serotonin-mediated regulation of dopamine release in the rat prefrontal cortex.
Endogenous serotonin (5-hydroxytryptamine, 5-HT)-mediated regulation of dopamine release in the rat prefrontal cortex was pharmacologically characterized using in vivo microdialysis. To increase synaptic 5-HT availability, a selective 5-HT uptake inhibitor fluoxetine was applied via the dialysis probe. Local perfusion of fluoxetine (30 and 100 microM) increased dopamine levels in a concentration-dependent manner. The fluoxetine (100 microM)-induced increases in dopamine release were abolished by pretreatment with the 5-HT(1B/1D) receptor antagonist GR 127935 (N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'-methyl-4'-(5- methyl-1,2,4-oxadiazol-3-yl)-[1,1-biphenyl]-4-carboxamide] ) (10 and 100 microM). The facilitation of dopamine release was also prevented by selective inactivation of the mRNA encoding 5-HT(6) receptors using antisense oligonucleotides techniques. These findings suggest that not only 5-HT(1B) receptors but also 5-HT(6) receptors are associated with the endogenous 5-HT-mediated facilitation of dopamine release. In other words, 5-HT(6) receptors may play, in part, a significant role in the functional interaction between the dopaminergic and serotonergic neuronal system in the rat prefrontal cortex.
Matsumoto
M
M
Department of Pharmacology, Hokkaido University School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, Japan. mbird@med.hokudai.ac.jp
Togashi
H
H
Mori
K
K
Ueno
K
K
Miyamoto
A
A
Yoshioka
M
M
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005473:Fluoxetine / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D011903:Raphe Nuclei / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects; D012701:Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology; D013997:Time Factors
D004298:Dopamine; D005473:Fluoxetine; D016376:Oligonucleotides, Antisense; D010069:Oxadiazoles; D010879:Piperazines; D011985:Receptors, Serotonin; D012701:Serotonin; D012702:Serotonin Antagonists; D017367:Selective Serotonin Reuptake Inhibitors; C097216:serotonin 6 receptor; C090701:GR 127935