Blockade of ionotropic glutamatergic transmission in the ventral tegmental area attenuates the physical signs of morphine withdrawal in rats.
The present study sought to assess whether the blockade of ionotropic glutamate receptors in the ventral tegmental area (VTA) could modulate the morphine withdrawal in male Sprague-Dawley rats. The effects of dizocilpine (MK-801) or 6,7-dinitroquinnoxaline-2,3-dione (DNQX), ionotropic glutamate receptor antagonists, microinjected unilaterally into the VTA 30 min before naloxone [2 mg/kg, intraperitoneally (i.p.)] administration on the morphine withdrawal were assessed. Morphine dependence was developed with increasing morphine injection (i.p.), and morphine withdrawal was induced by injection of naloxone (2 mg/kg, i.p.). Jumping, wet-dog shakes, writhing posture, wall clamber, weight loss and Gellert-Holtzman scale were used as the indices to evaluate the intensity of morphine withdrawal. The results showed that unilateral microinjection of MK-801 or DNQX into the VTA significantly increased the incidence of wall clamber, had no effect on weight loss, and reduced all other symptoms of morphine withdrawal. These data suggest that the ionotropic glutamate receptors in the VTA are involved in mediating naloxone-precipitated opiate withdrawal.
Wang
Hui-Ling
HL
Department of Physiology, School of Medicine, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
Zhao
Yan
Y
Xiang
Xiao-Hui
XH
Wang
Hui-Sheng
HS
Wu
Wei-Ran
WR
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D008845:Microinjections; D009020:Morphine / Q000009:adverse effects*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000009:adverse effects*; D011810:Quinoxalines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000523:psychology*; D009435:Synaptic Transmission / Q000187:drug effects*; D017557:Ventral Tegmental Area / Q000187:drug effects*; D015431:Weight Loss / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D011810:Quinoxalines; D017470:Receptors, Glutamate; D009270:Naloxone; C056723:FG 9041; D016291:Dizocilpine Maleate; D009020:Morphine