PMID- 12388654
OWN - NLM
STAT- MEDLINE
DCOM- 20021122
LR  - 20131121
IS  - 0022-3565 (Print)
IS  - 0022-3565 (Linking)
VI  - 303
IP  - 2
DP  - 2002 Nov
TI  - GABAergic and glutamatergic afferents in the dorsal raphe nucleus mediate 
      morphine-induced increases in serotonin efflux in the rat central nervous system.
PG  - 704-10
AB  - To characterize the effects of morphine on serotonin (5-HT) in the central 
      nervous system, we used microdialysis in freely behaving rats. Subcutaneous 
      injection of morphine sulfate produced a dose-dependent increase in extracellular 
      5-HT in the dorsal raphe nucleus (DRN) and a forebrain site, the nucleus 
      accumbens (NAcc). To determine the site of action for this effect, the opioid 
      receptor antagonist naltrexone was infused into either the DRN or NAcc. 
      Naltrexone infusion (300 microM) into the DRN but not the NAcc attenuated the 
      increase in 5-HT elicited by systemic morphine (20 mg/kg). This suggests that 
      morphine acts in the DRN to alter the activity of 5-HT neurons that project to 
      NAcc. Consistent with this conclusion, infusion of the GABA(A) receptor 
      antagonist bicuculline (100 microM) into the DRN but not the NAcc also blocked 
      the effect of systemic morphine. Similarly, the effect of systemic morphine was 
      blocked by infusion into the DRN of the GABA(A) receptor agonist muscimol (30 
      microM) and attenuated by the GABA(B) receptor agonist (+/-)-baclofen (100 
      microM). This provides evidence that morphine indirectly influences 5-HT release 
      via opioid receptors on GABAergic neurons in the DRN. A new finding is that 
      ionotropic glutamate receptor antagonists [kynurenate or a mixture of 
      (+/-)-2-amino-5-phosphonopentanoic acid and 6,7-dinitro-quinoxaline-2,3-dione] 
      infused in the DRN also attenuated the effect of systemic morphine. These results 
      suggest that morphine acts on GABAergic and glutamatergic afferents to indirectly 
      influence the activity of 5-HT neurons in the DRN. Understanding the details of 
      this neural circuitry may provide new leads for treatment of opiate addiction.
FAU - Tao, Rui
AU  - Tao R
AD  - Department of Cell Biology and Neuroscience, Rutgers University, Piscataway, New 
      Jersey, USA. rtao@hms.harvard.edu
FAU - Auerbach, Sidney B
AU  - Auerbach SB
LA  - eng
GR  - DA 14541/DA/NIDA NIH HHS/United States
GR  - MH 51080/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Pharmacol Exp Ther
JT  - The Journal of pharmacology and experimental therapeutics
JID - 0376362
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (GABA Agonists)
RN  - 0 (GABA-A Receptor Agonists)
RN  - 0 (Narcotic Antagonists)
RN  - 0 (Receptors, Glutamate)
RN  - 2763-96-4 (Muscimol)
RN  - 333DO1RDJY (Serotonin)
RN  - 3KX376GY7L (Glutamic Acid)
RN  - 56-12-2 (gamma-Aminobutyric Acid)
RN  - 5S6W795CQM (Naltrexone)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/*pharmacology
MH  - Animals
MH  - Central Nervous System/drug effects/*metabolism
MH  - Excitatory Amino Acid Agonists/administration & dosage/pharmacology
MH  - GABA Agonists/administration & dosage/pharmacology
MH  - GABA-A Receptor Agonists
MH  - Glutamic Acid/*physiology
MH  - Male
MH  - Microdialysis
MH  - Microinjections
MH  - Morphine/*pharmacology
MH  - Muscimol/administration & dosage/pharmacology
MH  - Naltrexone/pharmacology
MH  - Narcotic Antagonists/pharmacology
MH  - Neurons, Afferent/*physiology
MH  - Nucleus Accumbens/physiology
MH  - Raphe Nuclei/cytology/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Glutamate/drug effects
MH  - Serotonin/*metabolism
MH  - gamma-Aminobutyric Acid/*physiology
EDAT- 2002/10/22 04:00
MHDA- 2002/11/26 04:00
CRDT- 2002/10/22 04:00
PHST- 2002/10/22 04:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/10/22 04:00 [entrez]
AID - 10.1124/jpet.102.038133 [doi]
PST - ppublish
SO  - J Pharmacol Exp Ther. 2002 Nov;303(2):704-10. doi: 10.1124/jpet.102.038133.