Morphine causes a delayed increase in glutamate receptor functioning in the nucleus accumbens core.
Enhanced excitatory neurotransmission in the mesocorticolimbic system may contribute to the persistence of addiction behaviour. Here, we demonstrated that glutamate-, N-methyl-D-aspartate (NMDA)- and alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)-induced [3H]-gamma-aminobutyric acid (GABA) release from superfused rat nucleus accumbens core slices is profoundly enhanced 3 weeks, but not 3 days, after a single s.c. morphine injection. This delayed increase in glutamate receptor functioning is associated with enhanced gene transcript levels of ionotropic NMDA and AMPA/kainate receptor subunits. These data reveal that morphine may progressively enhance glutamate neurotransmission within the nucleus accumbens core subsequent to drug exposure.
Jacobs
Edwin H
EH
Research Institute Neurosciences Vrije Universiteit, Drug Abuse Program, Department of Medical Pharmacology, Free University Medical Center, VUmc, Van der Boechorststraat 7, 1081 BT Amsterdam, The Netherlands.
Wardeh
George
G
Smit
August B
AB
Schoffelmeer
Anton N M
AN
D000818:Animals; D018698:Glutamic Acid / Q000494:pharmacology; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000494:pharmacology; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D014316:Tritium; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D012333:RNA, Messenger; D017470:Receptors, Glutamate; D014316:Tritium; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D009020:Morphine; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D011188:Potassium