Stimulation by neurotensin of dopamine and 5-hydroxytryptamine (5-HT) release from rat prefrontal cortex: possible role of NTR1 receptors in neuropsychiatric disorders.
The modulation of cortical dopaminergic and serotonergic neurotransmissions by neurotensin (NT) was studied by measuring the release of dopamine (DA) and 5-hydroxytryptamine (5-HT) from the prefrontal cortex (PFC) of freely moving rats. The samples were collected via transversal microdialysis. Dopamine and 5-HT levels in the dialysate were measured using high-performance liquid chromatography (HPLC) with an electrochemical detector. Local administration of neurotensin (1microM or 0.1microM) in the PFC via the dialysis probe produced significant, long-lasting, and concentration-dependent increase in the extracellular release of DA and 5-HT. The increase produced by 1microM neurotensin reached a maximum of about 210% for DA and 340% for 5-HT. A high-affinity selective neurotensin receptor (NTR1) antagonist {2-[(1-(7-chloro-4-quinolinyl)-5-(2,6-dimethoxyphenyl)pyrazol-3yl)carbonylamino tricyclo (3.3.1.1.(3.7)) decan-2-carboxylic acid} (SR 48692), perfused locally at a concentration of 0.1microM and 0.5microM in the PFC antagonized the effects of 1microM neurotensin. Our in vivo neurochemical results indicate, for the first time, that neurotensin is able to regulate cortical dopaminergic and serotonergic neuronal activity in freely moving rats. These effects are possibly mediated by interactions of neurotensin with neurons releasing DA or 5-HT, projecting to the PFC from the ventrotegmental area (VTA) and from the dorsal raphe nuclei (DRN), respectively. The potentiating effects of neurotensin on DA and 5-HT release in the PFC are regulated by NTR1 receptors, probably located on dopaminergic and serotonergic nerve terminals or axons.
Institute of Biophysics, Bulgarian Academy of Sciences, Acad. G. Bonchev Street bl. 21, 1113 Sofia, Bulgaria.
Polina
P
Petkova-Kirova
Angelina
A
Rakovska
Galina
G
Zaekova
Chiara
C
Ballini
Laura Della
LD
Corte
Radomir
R
Radomirov
Anikó
A
Vágvölgyi
D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D008297:Male; D017551:Microdialysis; D009434:Neural Pathways / Q000187:drug effects / Q000378:metabolism; D019965:Neurocognitive Disorders / Q000378:metabolism / Q000503:physiopathology; D009496:Neurotensin / Q000378:metabolism* / Q000494:pharmacology; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism*; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism
D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C114036:neurotensin type 1 receptor; C079087:SR 48692; D012701:Serotonin; D009496:Neurotensin; D004298:Dopamine