Abstract | INTRODUCTION: METHODS: To explore the mechanisms of action of QTP, we determined its effects on extracellular levels of norepinephrine, dopamine, serotonin, gamma-aminobutyric acid ( GABA), and glutamate in the medial prefrontal cortex (mPFC) using microdialysis, and neuronal firing in the ventral tegmental area (VTA), locus coeruleus (LC), dorsal raphe nucleus (DRN), and mediodorsal thalamic nucleus (MTN) by telemetry in freely moving rats. RESULTS: DISCUSSION: The dopaminergic terminal projecting from the VTA received inhibitory GABA-mediated NMDA/glutamatergic regulation, but not stimulatory AMPA/glutamatergic regulation. However, both dopaminergic and noradrenergic terminals from the LC received stimulatory AMPA/glutamatergic regulation from the MTN, but not inhibitory GABA-mediated NMDA/glutamatergic regulation. These findings correlating neuronal activities in nuclei with neurotransmitter release suggested that the effects of QTP on neurotransmission in the mPFC depend on activated neuronal projections located outside the mPFC. Furthermore, positive interaction between LC and MTN afferents are potentially important in the pharmacological mechanisms of neurotransmitter regulation by QTP and hint at mechanisms underlying the atypical profile of this drug for treatment of schizophrenia and as a mood stabilizer and proconvulsive agent.
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Authors | Satoshi Yamamura, Keiko Ohoyama, Tatsuya Hamaguchi, Kanae Kashimoto, Masanori Nakagawa, Shinichi Kanehara, Dai Suzuki, Takuya Matsumoto, Eishi Motomura, Takashi Shiroyama, Motohiro Okada |
Journal | Psychopharmacology
(Psychopharmacology (Berl))
Vol. 206
Issue 2
Pg. 243-58
(Oct 2009)
ISSN: 1432-2072 [Electronic] Germany |
PMID | 19575183
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Antipsychotic Agents
- Biogenic Monoamines
- Dibenzothiazepines
- Excitatory Amino Acid Antagonists
- Quinoxalines
- Quetiapine Fumarate
- Glutamic Acid
- gamma-Aminobutyric Acid
- FG 9041
- Dizocilpine Maleate
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Topics |
- Action Potentials
(drug effects)
- Analysis of Variance
- Animals
- Antipsychotic Agents
(pharmacology)
- Biogenic Monoamines
(metabolism)
- Chromatography, Liquid
(methods)
- Dibenzothiazepines
(pharmacology)
- Dizocilpine Maleate
(pharmacology)
- Dose-Response Relationship, Drug
- Drug Interactions
- Excitatory Amino Acid Antagonists
(pharmacology)
- Glutamic Acid
(metabolism)
- Male
- Microdialysis
(methods)
- Neurons
(drug effects)
- Prefrontal Cortex
(cytology, drug effects, metabolism)
- Quetiapine Fumarate
- Quinoxalines
(pharmacology)
- Rats
- Rats, Sprague-Dawley
- Time Factors
- gamma-Aminobutyric Acid
(metabolism)
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