PMID- 9204911
OWN - NLM
STAT- MEDLINE
DCOM- 19970721
LR  - 20220408
IS  - 0270-6474 (Print)
IS  - 1529-2401 (Electronic)
IS  - 0270-6474 (Linking)
VI  - 17
IP  - 14
DP  - 1997 Jul 15
TI  - A postsynaptic interaction between dopamine D1 and NMDA receptors promotes 
      presynaptic inhibition in the rat nucleus accumbens via adenosine release.
PG  - 5271-80
AB  - The mechanism underlying dopamine D1 receptor-mediated attenuation of 
      glutamatergic synaptic input to nucleus accumbens (NAcc) neurons was investigated 
      in slices of rat forebrain, using whole-cell patch-clamp recording. The 
      depression by dopamine of EPSCs evoked by single-shock cortical stimulation was 
      stimulus-dependent. Synaptic activation of NMDA-type glutamate receptors was 
      critical for this effect, because dopamine-induced EPSC depressions were blocked 
      by the competitive NMDA receptor antagonist D/L-2-amino-5-phosphonopentanoate 
      (AP5). Application of NMDA also depressed the EPSC, and both this effect and the 
      dopamine depressions were blocked by the A1 receptor antagonist 
      8-cyclopentyl-1,3-dipropylxanthine (DPCPX), implicating adenosine release in the 
      EPSC depression. A1 receptor agonists also depressed EPSCs by a presynaptic 
      action, causing increased paired-pulse facilitation, but this was insensitive to 
      AP5. Activation of D1 receptors enhanced both postsynaptic inward currents evoked 
      by NMDA application and the isolated NMDA receptor-mediated component of synaptic 
      transmission. The biochemical processes underlying the dopamine-induced EPSC 
      depression did not involve either protein kinase A or the production of cAMP and 
      its metabolites, because this effect was resistant to the protein kinase 
      inhibitors H89 and H7 and the cAMP-specific phosphodiesterase inhibitor rolipram. 
      We conclude that activation of postsynaptic D1 receptors enhances the synaptic 
      activation of NMDA receptors in nucleus accumbens neurons, thereby promoting a 
      transsynaptic feedback inhibition of glutamatergic synaptic transmission via 
      release of adenosine. Unusually for D1 receptors, this phenomenon occurs 
      independently of adenylyl cyclase stimulation. This process may contribute to the 
      locomotor stimulant action of dopaminergic agents in the NAcc.
FAU - Harvey, J
AU  - Harvey J
AD  - Department of Pharmacology, The Medical School, University of Birmingham, 
      Edgbaston, Birmingham B15 2TT, United Kingdom.
FAU - Lacey, M G
AU  - Lacey MG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Neurosci
JT  - The Journal of neuroscience : the official journal of the Society for 
      Neuroscience
JID - 8102140
RN  - 0 (Receptors, Dopamine D1)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 76726-92-6 (2-Amino-5-phosphonovalerate)
RN  - K72T3FS567 (Adenosine)
RN  - VTD58H1Z2X (Dopamine)
SB  - IM
MH  - 2-Amino-5-phosphonovalerate/pharmacology
MH  - Adenosine/*metabolism
MH  - Animals
MH  - Dopamine/pharmacology
MH  - Male
MH  - Nucleus Accumbens/drug effects/*physiology
MH  - Rats
MH  - Rats, Wistar
MH  - Receptors, Dopamine D1/drug effects/*physiology
MH  - Receptors, N-Methyl-D-Aspartate/drug effects/*physiology
MH  - Synaptic Transmission/drug effects/*physiology
PMC - PMC6793812
EDAT- 1997/07/15 00:00
MHDA- 1997/07/15 00:01
PMCR- 1998/01/15
CRDT- 1997/07/15 00:00
PHST- 1997/07/15 00:00 [pubmed]
PHST- 1997/07/15 00:01 [medline]
PHST- 1997/07/15 00:00 [entrez]
PHST- 1998/01/15 00:00 [pmc-release]
AID - 10.1523/JNEUROSCI.17-14-05271.1997 [doi]
PST - ppublish
SO  - J Neurosci. 1997 Jul 15;17(14):5271-80. doi: 10.1523/JNEUROSCI.17-14-05271.1997.