Involvement of glutamate receptors within the central nucleus of the amygdala in naloxone-precipitated morphine withdrawal-induced conditioned place aversion in rats.
Chronic use of morphine leads to physical and psychological dependence. The amygdala is known to be involved in the expression of emotion such as anxiety and fear, and several studies have shown that the central nucleus of the amygdala (CeA) is involved in morphine dependence. In the present study, we investigated the role of glutamate receptors within the CeA in the negative affective component of morphine abstinence by evaluating naloxone-precipitated withdrawal-induced conditioned place aversion (CPA) in morphine-dependent rats. We found that microinjection of the AMPA/kainate-glutamate-receptor antagonist CNQX (30 nmol/side) into the bilateral CeA significantly attenuated the naloxone-precipitated withdrawal-induced CPA, as well as several somatic signs, in morphine-dependent rats, without preference or aversive effects by itself in non-dependent rats. Furthermore, microinjection of the non-competitive NMDA-receptor antagonist MK-801 (30 nmol/side) or competitive NMDA-receptor antagonist D-CPPene (0.01 and 0.1 nmol/side) into the CeA significantly attenuated the naloxone-precipitated morphine withdrawal-induced CPA, but not somatic withdrawal signs. These results suggest that the activation of AMPA /kainate and NMDA receptors within the CeA play a crucial role in the negative affective component of morphine abstinence.
Watanabe
Takeshi
T
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan.
Nakagawa
Takayuki
T
Yamamoto
Rie
R
Maeda
Akifumi
A
Minami
Masabumi
M
Satoh
Masamichi
M
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000008:administration & dosage / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D002529:Cerebellar Nuclei / Q000502:physiology; D003213:Conditioning, Psychological; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000009:adverse effects*; D009021:Morphine Dependence / Q000378:metabolism* / Q000523:psychology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009294:Narcotics / Q000009:adverse effects*; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects* / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000523:psychology
D018691:Excitatory Amino Acid Antagonists; D009292:Narcotic Antagonists; D009294:Narcotics; D010879:Piperazines; D017470:Receptors, Glutamate; C065286:SDZ EAA 494; D009270:Naloxone; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D009020:Morphine