PMID- 15610184
OWN - NLM
STAT- MEDLINE
DCOM- 20050215
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 20
IP  - 12
DP  - 2004 Dec
TI  - Blocking the R-type (Cav2.3) Ca2+ channel enhanced morphine analgesia and reduced 
      morphine tolerance.
PG  - 3516-9
AB  - Morphine is the drug of choice to treat intractable pain, although prolonged 
      administration often causes undesirable side-effects including analgesic 
      tolerance. It is speculated that voltage-dependent Ca(2+) channels (VDCCs) play a 
      key role in morphine analgesia and tolerance. To examine the subtype specificity 
      of VDCCs in these processes, we analysed mice lacking N-type (Ca(v)2.2) or R-type 
      (Ca(v)2.3) VDCCs. Systemic morphine administration or exposure to warm water 
      swim-stress, known to induce endogenous opioid release, resulted in greater 
      analgesia in Ca(v)2.3(-/-) mice than in controls. Moreover, Ca(v)2.3(-/-) mice 
      showed resistance to morphine tolerance. In contrast, Ca(v)2.2(-/-) mice showed 
      similar levels of analgesia and tolerance to control mice. 
      Intracerebroventricular (i.c.v.) but not intrathecal (i.t.) administration of 
      morphine reproduced the result of systemic morphine in Ca(v)2.3(-/-) mice. 
      Furthermore, i.c.v. administration of an R-type channel blocker potentiated 
      morphine analgesia in wild-type mice. Thus, the inhibition of R-type Ca(2+) 
      current could lead to high-efficiency opioid therapy without tolerance.
FAU - Yokoyama, Kazuaki
AU  - Yokoyama K
AD  - Department of Pharmacology and Neurobiology, Graduate School of Medicine, Tokyo 
      Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
FAU - Kurihara, Takashi
AU  - Kurihara T
FAU - Saegusa, Hironao
AU  - Saegusa H
FAU - Zong, Shuqin
AU  - Zong S
FAU - Makita, Koshi
AU  - Makita K
FAU - Tanabe, Tsutomu
AU  - Tanabe T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Analgesics, Opioid)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels, R-Type)
RN  - 76I7G6D29C (Morphine)
SB  - IM
MH  - Analgesics, Opioid/*pharmacology
MH  - Animals
MH  - Calcium Channel Blockers/*pharmacology
MH  - Calcium Channels, R-Type/genetics/*metabolism/physiology
MH  - Drug Tolerance/physiology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Mice, Mutant Strains
MH  - Morphine/*pharmacology
MH  - Pain Measurement/*drug effects/methods
EDAT- 2004/12/22 09:00
MHDA- 2005/02/16 09:00
CRDT- 2004/12/22 09:00
PHST- 2004/12/22 09:00 [pubmed]
PHST- 2005/02/16 09:00 [medline]
PHST- 2004/12/22 09:00 [entrez]
AID - EJN3810 [pii]
AID - 10.1111/j.1460-9568.2004.03810.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2004 Dec;20(12):3516-9. doi: 10.1111/j.1460-9568.2004.03810.x.