Ionotropic glutamatergic neurotransmission in the ventral tegmental area modulates DeltaFosB expression in the nucleus accumbens and abstinence syndrome in morphine withdrawal rats.
The present study sought to assess whether the blockade of ionotropic glutamate receptors in the ventral tegmental area could modulate morphine withdrawal in morphine-dependent rats and the expression of stable DeltaFosB isoforms in the nucleus accumbens during morphine withdrawal. Rats were injected (i.p.) with increasing doses of morphine for 1 week to develop physical dependence, and withdrawal was then precipitated by one injection of naloxone (2 mg/kg, i.p.). Abstinence signs such as jumping, wet-dog shake, writhing posture, weight loss, and Gellert-Holtzman scale score were recorded to evaluate naloxone-induced morphine withdrawal. Two ionotropic glutamate receptor antagonists, dizocilpine (MK-801) and 6, 7-dinitroquinnoxaline-2, 3-dione (DNQX), were microinjected unilaterally into the ventral tegmental area 30 min before naloxone precipitation. A second injection of naloxone (2 mg/kg i.p.) was given 1 h after the first naloxone injection to sustain a maximal level of withdrawal so that the expression of stable DeltaFosB isoforms in the nucleus accumbens could be measured. This would enable determination of the correlation between the MK-801 or DNQX-induced decrease in somatic withdrawal signs and the change in neuronal activity in the nucleus accumbens. The results showed that both MK-801 and DNQX significantly alleviated all symptoms of morphine withdrawal except for weight loss and reduced the expression of stable DeltaFosB isoforms within the nucleus accumbens. These data suggest that ionotropic glutamatergic neurotransmission in the ventral tegmental area regulates the levels of stable DeltaFosB isoforms in the nucleus accumbens, which play a very important role in modulating opiate withdrawal.
Wang
Hui-Ling
HL
Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Xi'an Jiaotong University, China. wanghuiling63@163.com
Xiang
Xiao-Hui
XH
Guo
Yuan
Y
Wu
Wei-Ran
WR
Cao
Dong-Yuan
DY
Wang
Hui-Sheng
HS
Zhao
Yan
Y
D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology / Q000627:therapeutic use; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology / Q000627:therapeutic use; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000008:administration & dosage / Q000633:toxicity; D009021:Morphine Dependence / Q000209:etiology / Q000503:physiopathology*; D009270:Naloxone / Q000008:administration & dosage; D009714:Nucleus Accumbens / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000175:diagnosis / Q000503:physiopathology / Q000517:prevention & control*; D009435:Synaptic Transmission / Q000502:physiology*; D017557:Ventral Tegmental Area / Q000737:chemistry / Q000187:drug effects / Q000502:physiology*
D018691:Excitatory Amino Acid Antagonists; C483820:Fosb protein, rat; D020033:Protein Isoforms; D016760:Proto-Oncogene Proteins c-fos; D011810:Quinoxalines; D016194:Receptors, N-Methyl-D-Aspartate; D009270:Naloxone; C056723:FG 9041; D016291:Dizocilpine Maleate; D009020:Morphine