PMID- 9137909
OWN - NLM
STAT- MEDLINE
DCOM- 19970724
LR  - 20191210
IS  - 0014-2999 (Print)
IS  - 0014-2999 (Linking)
VI  - 324
IP  - 1
DP  - 1997 Apr 11
TI  - Differential effects of mu-, delta- and kappa-opioid receptor agonists on the 
      discriminative stimulus properties of cocaine in rats.
PG  - 21-9
AB  - The effects of selective mu-, delta- and kappa-opioid receptor agonists on the 
      discriminative stimulus properties of cocaine were examined in rats trained to 
      discriminate between cocaine (10 mg/kg) and saline. Cocaine produced a 
      dose-related increase in cocaine-appropriate responses in all of the rats. In 
      generalization tests, neither morphine (mu-opioid receptor agonist) nor 
      N-methyl-N-7-(1-pyrrolidinyl)-1-oxaspiro[4,5]dec-8-11-4-benzofu ranacetamide 
      (U50,488H: kappa-opioid receptor agonist) generalized to the discriminative 
      stimulus properties of cocaine. On the other hand, the newly synthesized 
      non-peptide selective delta-opioid receptor agonist 2-methyl-4a 
      alpha-(3-hydroxyphenyl)-1,2,3,4,4a,5,12,12a 
      alpha-octahydro-quinolino(2,3,3,-g)isoquinoline (TAN-67) partially generalized 
      (56.7% cocaine-appropriate responses) to the discriminative stimulus properties 
      of cocaine. Intracerebroventricular (i.c.v.) administration of [D-Ala2]deltorphin 
      II (peptide delta 2-opioid receptor agonist) completely generalized, while 
      neither [D-Ala2,MePhe4,Gly-ol5]enkephalin (DAMGO: mu-opioid receptor agonist) nor 
      [D-Pen2,D-Pen5]enkephalin (DPDPE; delta 1-opioid receptor agonist) generalized to 
      the discriminative stimulus properties of cocaine. These results suggest that the 
      discriminative stimulus properties of cocaine may be partially mediated by 
      delta-opioid (especially delta 2-opioid) receptors. In combination tests, 
      pretreatment with morphine (3.0 mg/kg) and TAN-67 (3.0 and 10 mg/kg) 
      significantly potentiated the discriminative stimulus properties cocaine. In 
      contrast, pretreatment with U50,488H (2.0 and 4.0 mg/kg) scarcely shifted the 
      discriminative stimulus properties of cocaine. Furthermore, the potentiating 
      effect of 3.0 mg/kg morphine on the discriminative stimulus properties of cocaine 
      was attenuated by 2.0 mg/kg U50,488H. In contrast, the potentiating effect of 10 
      mg/kg TAN-67 on the discriminative stimulus properties of cocaine was not 
      reversed by either 2.0 or 4.0 mg/kg U50,488H. These results suggest that mu-, 
      delta- and kappa-opioid receptor agonists modulate the discriminative stimulus 
      properties of cocaine through different mechanisms, perhaps through different 
      effects on the dopaminergic system.
FAU - Suzuki, T
AU  - Suzuki T
AD  - Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
FAU - Mori, T
AU  - Mori T
FAU - Tsuji, M
AU  - Tsuji M
FAU - Maeda, J
AU  - Maeda J
FAU - Kishimoto, Y
AU  - Kishimoto Y
FAU - Misawa, M
AU  - Misawa M
FAU - Nagase, H
AU  - Nagase H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Analgesics)
RN  - 0 (Enkephalins)
RN  - 0 (Narcotics)
RN  - 0 (Pyrrolidines)
RN  - 0 (Quinolines)
RN  - 0 (Receptors, Opioid, delta)
RN  - 0 (Receptors, Opioid, kappa)
RN  - 0 (Receptors, Opioid, mu)
RN  - 0 (TAN 67)
RN  - 100929-53-1 (Enkephalin, Ala(2)-MePhe(4)-Gly(5)-)
RN  - 67198-13-4 
      (3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer)
RN  - 76I7G6D29C (Morphine)
RN  - 88373-73-3 (Enkephalin, D-Penicillamine (2,5)-)
RN  - I5Y540LHVR (Cocaine)
SB  - IM
MH  - 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, 
      (trans)-Isomer
MH  - Analgesics/administration & dosage/pharmacology
MH  - Analysis of Variance
MH  - Animals
MH  - Cocaine/administration & dosage/*toxicity
MH  - Discrimination Learning/*drug effects
MH  - Discrimination, Psychological/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
MH  - Enkephalin, D-Penicillamine (2,5)-
MH  - Enkephalins/administration & dosage/pharmacology
MH  - Injections, Intraventricular
MH  - Male
MH  - Morphine/administration & dosage/toxicity
MH  - Narcotics/administration & dosage/*toxicity
MH  - Pyrrolidines/administration & dosage/pharmacology
MH  - Quinolines/administration & dosage/pharmacology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, Opioid, delta/*agonists
MH  - Receptors, Opioid, kappa/*agonists
MH  - Receptors, Opioid, mu/*agonists
MH  - Substance-Related Disorders
EDAT- 1997/04/11 00:00
MHDA- 1997/04/11 00:01
CRDT- 1997/04/11 00:00
PHST- 1997/04/11 00:00 [pubmed]
PHST- 1997/04/11 00:01 [medline]
PHST- 1997/04/11 00:00 [entrez]
AID - S0014-2999(97)00062-9 [pii]
AID - 10.1016/s0014-2999(97)00062-9 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 1997 Apr 11;324(1):21-9. doi: 10.1016/s0014-2999(97)00062-9.