PMID- 19682375
OWN - NLM
STAT- MEDLINE
DCOM- 20090929
LR  - 20220309
IS  - 1471-2202 (Electronic)
IS  - 1471-2202 (Linking)
VI  - 10
DP  - 2009 Aug 14
TI  - Presynaptic action of neurotensin on dopamine release through inhibition of D(2) 
      receptor function.
PG  - 96
LID - 10.1186/1471-2202-10-96 [doi]
AB  - BACKGROUND: Neurotensin (NT) is known to act on dopamine (DA) neurons at the 
      somatodendritic level to regulate cell firing and secondarily enhance DA release. 
      In addition, anatomical and indirect physiological data suggest the presence of 
      NT receptors at the terminal level. However, a clear demonstration of the 
      mechanism of action of NT on dopaminergic axon terminals is lacking. We 
      hypothesize that NT acts to increase DA release by inhibiting the function of 
      terminal D2 autoreceptors. To test this hypothesis, we used fast-scan cyclic 
      voltammetry (FCV) to monitor in real time the axonal release of DA in the nucleus 
      accumbens (NAcc). RESULTS: DA release was evoked by single electrical pulses and 
      pulse trains (10 Hz, 30 pulses). Under these two stimulation conditions, we 
      evaluated the characteristics of DA D2 autoreceptors and the presynaptic action 
      of NT in the NAcc shell and shell/core border region. The selective agonist of D2 
      autoreceptors, quinpirole (1 microM), inhibited DA overflow evoked by both single 
      and train pulses. In sharp contrast, the selective D2 receptor antagonist, 
      sulpiride (5 microM), strongly enhanced DA release triggered by pulse trains, 
      without any effect on DA release elicited by single pulses, thus confirming 
      previous observations. We then determined the effect of NT (8-13) (100 nM) and 
      found that although it failed to increase DA release evoked by single pulses, it 
      strongly enhanced DA release evoked by pulse trains that lead to prolonged DA 
      release and engage D2 autoreceptors. In addition, initial blockade of D2 
      autoreceptors by sulpiride considerably inhibited further facilitation of DA 
      release generated by NT (8-13). CONCLUSION: Taken together, these data suggest 
      that NT enhances DA release principally by inhibiting the function of terminal D2 
      autoreceptors and not by more direct mechanisms such as facilitation of terminal 
      calcium influx.
FAU - Fawaz, Charbel S
AU  - Fawaz CS
AD  - Department of Pharmacology, Groupe de Recherche sur le Systeme Nerveux Central, 
      Faculty of Medicine, Universite de Montreal, Quebec, H3C 3J7, Canada. 
      charbelf@total.net
FAU - Martel, Philippe
AU  - Martel P
FAU - Leo, Damiana
AU  - Leo D
FAU - Trudeau, Louis-Eric
AU  - Trudeau LE
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090814
PL  - England
TA  - BMC Neurosci
JT  - BMC neuroscience
JID - 100966986
RN  - 0 (Autoreceptors)
RN  - 0 (Dopamine Agonists)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Receptors, Dopamine D2)
RN  - 0 (Receptors, Neurotensin)
RN  - 0 (Receptors, Presynaptic)
RN  - 20OP60125T (Quinpirole)
RN  - 39379-15-2 (Neurotensin)
RN  - 7MNE9M8287 (Sulpiride)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - Animals
MH  - Autoreceptors/physiology
MH  - Dopamine/*physiology
MH  - Dopamine Agonists/pharmacology
MH  - Dopamine Antagonists/pharmacology
MH  - Electric Stimulation
MH  - Electrochemistry
MH  - Exocytosis/*drug effects/physiology
MH  - In Vitro Techniques
MH  - Neurotensin/*pharmacology
MH  - Nucleus Accumbens/drug effects/physiology
MH  - Presynaptic Terminals/drug effects/physiology
MH  - Quinpirole/pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Dopamine D2/*physiology
MH  - Receptors, Neurotensin/physiology
MH  - Receptors, Presynaptic/physiology
MH  - Sulpiride/pharmacology
MH  - Synaptic Transmission/*drug effects
PMC - PMC2745416
EDAT- 2009/08/18 09:00
MHDA- 2009/09/30 06:00
PMCR- 2009/08/14
CRDT- 2009/08/18 09:00
PHST- 2008/10/08 00:00 [received]
PHST- 2009/08/14 00:00 [accepted]
PHST- 2009/08/18 09:00 [entrez]
PHST- 2009/08/18 09:00 [pubmed]
PHST- 2009/09/30 06:00 [medline]
PHST- 2009/08/14 00:00 [pmc-release]
AID - 1471-2202-10-96 [pii]
AID - 10.1186/1471-2202-10-96 [doi]
PST - epublish
SO  - BMC Neurosci. 2009 Aug 14;10:96. doi: 10.1186/1471-2202-10-96.