title: Mirtazapine increases dopamine release in prefrontal cortex by 5-HT1A receptor activation.
abstract: Mirtazapine has a low affinity for 5-HT(1A) receptors but shows 5-HT(1A)-agonistic-like effects in behavioral pharmacology test. However, there is to date no clear evidence that mirtazapine enhances 5-HT(1A) neurotransmission. The object of the present study was to assess the effects of mirtazapine on dialysate levels of dopamine and 5-HT in the medial frontal cortex of freely moving rats and to determine whether this drug could modulate 5-HT(1A) neurotransmission. In vivo microdialysis was used to study the effects of mirtazapine on extracellular dopamine and 5-HT levels, and the effect of the 5-HT(1A) antagonist WAY100,356 on extracellular dopamine level increased by mirtazapine in the rat prefrontal cortex. Mirtazapine (4-16 mg/kg, i.p.) produced a dose-dependent increase in extracellular dopamine levels in the medial prefrontal cortex (mPFC) of freely moving rats without modifying those of 5-HT. In the presence of the selective 5-HT(1A) receptor antagonist N-[2-[4-(2-methoxyphenyl)-1-piperazineyl]ethyl]-N-(pyridinyl)-cyclohexane-carboxamide (WAY100,635; 0.3 mg/kg; i.p.), the influence of mirtazapine on cortical levels of dopamine was markedly attenuated. These results indicate that mirtazapine induces the enhancement of the output of cortical dopamine mediated via blockade of alpha(2)-adrenergic receptors and facilitation of post-synaptic 5-HT(1A) function.
authors.affiliation: Department of Psychiatry, Jikei University School of Medicine, 3-25-8 Nishi Shinbashi, Minato-ku, Tokyo 105-8461, Japan. Kazu-n@yb3.so-net.ne.jp
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Nakayama
authors.forename: Takashi
authors.initials: T
authors.lastname: Sakurai
authors.forename: Hisatoshi
authors.initials: H
authors.lastname: Katsu
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects; D004298:Dopamine / Q000032:analysis* / Q000378:metabolism; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D008297:Male; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017551:Microdialysis; D000078785:Mirtazapine; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044282:Receptor, Serotonin, 5-HT1A / Q000187:drug effects* / Q000378:metabolism
chemical_list: D000929:Antidepressive Agents, Tricyclic; D018492:Dopamine Antagonists; D044282:Receptor, Serotonin, 5-HT1A; D008803:Mianserin; D000078785:Mirtazapine; D004298:Dopamine