Morphine releases glutamate through AMPA receptors in the ventral tegmental area: a microdialysis study in conscious rats

ABSTRACT

In vivo microdialysis was used to study the effects of morphine on glutamate release from the ventral tegmentum area [VTA] in freely moving rats. Intraperitoneal [i.p.] injection of acute and repeated morphine at increasing doses significantly enhanced glutamate release. Only a minor tolerance developed to this dosage of morphine. AP-5 [2-amino-5-phosphonovaleric acid, 0.5 mg/kg i.p.], a NMDA receptor antagonist, given 20 min before each repeated morphine injection, did not have a significant effect on the stimulated glutamate release. Conversely, injection of CNQX [6-cyano-7-nitroquinoxaline-2, 3-dione, 0.5 mg/kg i.p.], an AMPA receptor antagonist, 20 min before each morphine dose was found to markedly inhibit morphine-induced glutamate release in the VTA. In all experiments, glutamate release reduced by time. These results show for the first time that acute and repeated injection of morphine stimulates glutamate release in the conscious rat VTA via AMPA receptors