Abstract
The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood. Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission. We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated. CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]cyclo- hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (±)-2-amino-3-phosphonopropionic acid (AP-3) and (±)-α- methyl-4-carboxyphenylglycine (4MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol. These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.
| Original language | English |
|---|---|
| Pages (from-to) | 751-757 |
| Number of pages | 7 |
| Journal | British Journal of Pharmacology |
| Volume | 145 |
| Issue number | 6 |
| DOIs | |
| Publication status | Published - Jul 2005 |
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Keywords
- Acute dependence
- Conditioned place aversion
- Dopamine
- Glutamate receptor antagonist
- Morphine
- Naloxone
- Withdrawal
ASJC Scopus subject areas
- Pharmacology
Cite this
Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats. / Kawasaki, Yoichi; Jin, Chunyu; Suemaru, Katsuya; Kawasaki, Hiromu; Shibata, Kazuhiko; Choshi, Tominari; Hibino, Satoshi; Gomita, Yutaka; Araki, Hiroaki.
In: British Journal of Pharmacology, Vol. 145, No. 6, 07.2005, p. 751-757.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effect of glutamate receptor antagonists on place aversion induced by naloxone in single-dose morphine-treated rats
AU - Kawasaki, Yoichi
AU - Jin, Chunyu
AU - Suemaru, Katsuya
AU - Kawasaki, Hiromu
AU - Shibata, Kazuhiko
AU - Choshi, Tominari
AU - Hibino, Satoshi
AU - Gomita, Yutaka
AU - Araki, Hiroaki
PY - 2005/7
Y1 - 2005/7
N2 - The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood. Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission. We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated. CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]cyclo- hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (±)-2-amino-3-phosphonopropionic acid (AP-3) and (±)-α- methyl-4-carboxyphenylglycine (4MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol. These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.
AB - The neurobiological mechanism underlying the negative motivational component of withdrawal from acute opiate dependence is far from understood. Our objectives were to determine whether the glutamatergic system is involved in the motivational component of morphine withdrawal in acutely dependent rats and such an involvement is associated with dopaminergic neurotransmission. We examined the effects of various kinds of glutamate receptor antagonists on conditioned place aversion (CPA) induced by naloxone-precipitated withdrawal from a single morphine exposure 24 h before. Furthermore, the influence of pretreatment with the dopamine receptor antagonist haloperidol on those effects of glutamate receptor antagonists was also investigated. CPA was attenuated in a dose-dependent manner by all glutamate receptor antagonists examined including the NMDA receptor antagonists (+)-5-methyl-10,11 -dihydro-5H-dibenzo[a,d]cyclo- hepten-5,10-imine maleate (MK-801) and phencyclidine hydrochloride (PCP), AMPA receptor antagonist 1-(4-aminophenyl)4-methyl-7,8-methylenedioxy-5H-2,3- benzodiazepine hydrochloride (GYKI 52466), and metabotropic receptor antagonists (±)-2-amino-3-phosphonopropionic acid (AP-3) and (±)-α- methyl-4-carboxyphenylglycine (4MCPG). The effects of MK-801, GYKI 52466 and MCPG were blocked by haloperidol. These results suggest that the glutamatergic system involving multiple classes of receptors plays a role in the motivational component of withdrawal from acute morphine dependence, and the function of the glutamatergic system would be closely associated with dopaminergic neurotransmission.
KW - Acute dependence
KW - Conditioned place aversion
KW - Dopamine
KW - Glutamate receptor antagonist
KW - Morphine
KW - Naloxone
KW - Withdrawal
UR - http://www.scopus.com/inward/record.url?scp=23044448530&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=23044448530&partnerID=8YFLogxK
U2 - 10.1038/sj.bjp.0706228
DO - 10.1038/sj.bjp.0706228
M3 - Article
C2 - 15880144
AN - SCOPUS:23044448530
VL - 145
SP - 751
EP - 757
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
SN - 0007-1188
IS - 6
ER -