PMID- 15571673
OWN - NLM
STAT- MEDLINE
DCOM- 20050308
LR  - 20181201
IS  - 0006-8993 (Print)
IS  - 0006-8993 (Linking)
VI  - 1030
IP  - 2
DP  - 2004 Dec 31
TI  - Involvement of kappa-opioid receptors and sigma receptors in memory function 
      demonstrated using an antisense strategy.
PG  - 247-55
AB  - Although antinociceptive effects of U-50,488H 
      (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl] cyclohexyl) 
      benzeneacetamide methanesulfonate and (-)-pentazocine have been reported to 
      influence kappa-opioid receptors, the involvement of kappa-opioid receptors in 
      learning and/or memory is still controversial. We have recently reported that the 
      memory improving effect of (-)-pentazocine was antagonized by sigma1 receptor 
      antagonist. In this study, we examined the effects of several antisense 
      oligodeoxynucleotides (antisenses) to kappa1-opioid receptors and sigma1 receptor 
      on memory and nociceptive function. Male ddY mice were treated subcutaneously 
      (s.c.) with scopolamine (1.65 mumol/kg) and/or test drugs 30 min before a Y-maze 
      test. U-50,488H significantly improved the scopolamine-induced impairment of 
      spontaneous alternation behavior. Twenty micrograms of antisense targeting exons 
      2 and 3 of the kappa1-opioid receptor significantly reversed the effects of 
      U-50,488H, but antisense targeting exon 1 and mismatch sense did not. The 
      antisense targeting exon 3 was most effective. These antisenses themselves did 
      not affect normal mice, indicating that kappa1-opioid receptors do not tonically 
      regulate memory function. All three antisenses equally prevented 
      U-50,488H-induced antinociceptive effects in the acetic-acid-induced writhing 
      test. Pretreatment with antisense targeting sigma1 receptors (AS-sigma1) 
      completely prevented the memory-improving effects of (-)- and (+)-pentazocine, 
      although U-50,488H ameliorated the scopolamine-induced impairment of spontaneous 
      alternation behavior in AS-sigma1-treated mice. These results suggest that 
      kappa1-opioid receptors containing different exons have a distinct function in 
      memory and nociceptive functions. Furthermore, kappa-opioid receptors agonist 
      showing analgesic effects act on kappa-opioid receptors or sigma receptors and 
      play important roles only when memory function is impaired, but the two neuronal 
      systems regulate memory function independently.
FAU - Hiramatsu, Masayuki
AU  - Hiramatsu M
AD  - Laboratory of Neuropsychopharmacology, Graduate School of Environmental and Human 
      Sciences, Meijo University, Tenpaku-ku, Nagoya 468-8503, Japan. 
      mhiramt@ccms.meijo-u.ac.jp
FAU - Hoshino, Takashi
AU  - Hoshino T
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Brain Res
JT  - Brain research
JID - 0045503
RN  - 0 (Analgesics, Non-Narcotic)
RN  - 0 (Oligodeoxyribonucleotides, Antisense)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 0 (Receptors, sigma)
RN  - 0 (kappa(1) opioid receptor)
RN  - 67198-13-4 
      (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer)
RN  - DL48G20X8X (Scopolamine)
SB  - IM
MH  - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer/pharmacology
MH  - Analgesics, Non-Narcotic/pharmacology
MH  - Animals
MH  - Exploratory Behavior/drug effects/*physiology
MH  - Male
MH  - Maze Learning/drug effects/*physiology
MH  - Memory Disorders/chemically induced
MH  - Memory, Short-Term/drug effects/*physiology
MH  - Mice
MH  - Nociceptors/drug effects/physiology
MH  - Oligodeoxyribonucleotides, Antisense
MH  - Receptors, Opioid, kappa/drug effects/*physiology
MH  - Receptors, sigma/*physiology
MH  - Scopolamine
EDAT- 2004/12/02 09:00
MHDA- 2005/03/09 09:00
CRDT- 2004/12/02 09:00
PHST- 2004/10/17 00:00 [accepted]
PHST- 2004/12/02 09:00 [pubmed]
PHST- 2005/03/09 09:00 [medline]
PHST- 2004/12/02 09:00 [entrez]
AID - S0006-8993(04)01685-3 [pii]
AID - 10.1016/j.brainres.2004.10.020 [doi]
PST - ppublish
SO  - Brain Res. 2004 Dec 31;1030(2):247-55. doi: 10.1016/j.brainres.2004.10.020.