PMID- 14684447
OWN - NLM
STAT- MEDLINE
DCOM- 20040213
LR  - 20190616
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1003
DP  - 2003 Nov
TI  - Glutamatergic transmission in opiate and alcohol dependence.
PG  - 196-211
AB  - Both the nucleus accumbens (NAcc) and central amygdala (CeA) are thought to play 
      roles in tolerance to, and dependence on, abused drugs. Although our past studies 
      in rat brain slices suggested a role for NMDA receptors (NMDARs) in NAcc neurons 
      in the effects of acute and chronic opiate treatment, the cellular and molecular 
      mechanisms remained unclear. Therefore, we examined the effects of morphine 
      dependence on electrophysiological properties of NMDARs in freshly isolated NAcc 
      neurons and on expression of mRNA coding for NR2A-C subunits using single-cell 
      RT-PCR. Chronic morphine did not alter the affinity for NMDAR agonists glutamate, 
      homoquinolinate, or NMDA, but decreased the affinity of the coagonist glycine. 
      Chronic morphine altered the NMDAR inhibition by two NMDAR antagonists, 
      7-Cl-kynurenate and ifenprodil, but not that by d-APV or Mg2+. Chronic morphine 
      accelerated the NMDA current desensitization rate in NAcc neurons. In single-cell 
      RT-PCR, chronic morphine predominantly reduced the number of neurons expressing 
      multiple NR2 subunits. Ethanol also alters NMDARs. We found that low ethanol 
      concentrations (IC50 = 13 mM) inhibited NMDA currents and NMDA-EPSPs in most NAcc 
      neurons in a slice preparation. NAcc neurons from ethanol-dependent rats showed 
      enhanced NMDA sensitivity. In CeA neurons, acute ethanol decreased (by 10-25%) 
      non-NMDA- and NMDA-EPSPs in most neurons. In CeA neurons from ethanol-dependent 
      rats, acute ethanol decreased the non-NMDA-EPSPs to the same extent as in naive 
      rats, but inhibited (by 30-40%) NMDA-EPSPs significantly more than in controls, 
      suggesting sensitization to ethanol. Preliminary studies with microdialysis and 
      real-time PCR analysis support this idea: local ethanol administration in vivo 
      had no effect on glutamate release, but chronic ethanol nearly tripled the 
      expression of NR2B subunits (the most ethanol sensitive) in CeA. These combined 
      findings suggest that changes in glutamatergic transmission in NAcc and CeA may 
      underlie the neuroadaptions that lead to opiate and ethanol dependence.
FAU - Siggins, George Robert
AU  - Siggins GR
AD  - Department of Neuropharmacology, Department of Molecular Biology, The Scripps 
      Research Institute, 10550 Torrey Pines Road, La Jolla, California 92037, USA. 
      geobob@scripps.edu
FAU - Martin, Gilles
AU  - Martin G
FAU - Roberto, Marisa
AU  - Roberto M
FAU - Nie, Zhiguo
AU  - Nie Z
FAU - Madamba, Samuel
AU  - Madamba S
FAU - De Lecea, Luis
AU  - De Lecea L
LA  - eng
GR  - AA06420/AA/NIAAA NIH HHS/United States
GR  - DA03665/DA/NIDA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PT  - Review
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Glutamates)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 3K9958V90M (Ethanol)
RN  - TE7660XO1C (Glycine)
SB  - IM
MH  - Alcoholism/*physiopathology
MH  - Amygdala/physiology
MH  - Animals
MH  - Ethanol/pharmacology
MH  - Glutamates/*physiology
MH  - Glycine/metabolism
MH  - Humans
MH  - Morphine Dependence/physiopathology
MH  - Neurons/drug effects/metabolism
MH  - Nucleus Accumbens/physiology
MH  - Opioid-Related Disorders/*physiopathology
MH  - Rats
MH  - Receptors, N-Methyl-D-Aspartate/biosynthesis/drug effects
MH  - Synaptic Transmission/drug effects/*physiology
RF  - 61
EDAT- 2003/12/20 05:00
MHDA- 2004/02/14 05:00
CRDT- 2003/12/20 05:00
PHST- 2003/12/20 05:00 [pubmed]
PHST- 2004/02/14 05:00 [medline]
PHST- 2003/12/20 05:00 [entrez]
AID - 10.1196/annals.1300.012 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2003 Nov;1003:196-211. doi: 10.1196/annals.1300.012.