Mu-opioid component of the ethylketocyclazocine (RKC) discriminative stimulus in the rat

The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the...

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Bibliographic Details
Published in:Psychopharmacologia 1989-01, Vol.99 (4), p.492-496
Main Authors: LOCKE, K. W, GORNEY, B, CORNFELDT, M, FIELDING, S
Format: Article
Language:English
Subjects:
3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
Analgesics
Animals
Biological and medical sciences
Cyclazocine - analogs & derivatives
Cyclazocine - pharmacology
Discrimination (Psychology) - drug effects
Dose-Response Relationship, Drug
Ethylketocyclazocine
Fentanyl - pharmacology
Male
Medical sciences
Morphine - pharmacology
Naloxone - pharmacology
Neuropharmacology
Pharmacology. Drug treatments
Pyrrolidines - pharmacology
Rats
Receptors, Opioid - physiology
Receptors, Opioid, mu
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Summary:The opioid receptor selectivity of the EKC discriminative stimulus was characterized in Fischer rats trained to discriminate 0.3 mg/kg EKC (SC) from saline in a two-choice discrete-trial avoidance paradigm. The putative kappa-opioid receptor agonists EKC and U50,488H completely generalized with the EKC cue at doses of 0.3 and 10 mg/kg, respectively. The putative mu-opioid receptor agonists morphine (M) and fentanyl also dose-dependently generalized with the EKC stimulus. The generalization of M with EKC was not symmetrical, EKC and U50,488H produced little or no M-appropriate responding in rats trained to discriminate 3.0 mg/kg M (SC) from saline. This generalization pattern may reflect a lack of opioid receptor selectivity of the EKC stimulus. However, distinct mu-opioid and kappa-opioid components of the EKC cue could be identified using graded doses of naloxone in EKC-trained rats. The discriminative effects of morphine and fentanyl were blocked completely by doses of 0.1-1.0 mg/kg naloxone, whereas doses of naloxone 3-10 times greater were necessary to block the discriminative effects of EKC and U50,488H. These results suggest that EKC produces a complex discriminative stimulus with mu-opioid and kappa-opioid components that can be separated using antagonists such as naloxone.
ISSN:0033-3158
1432-2072
DOI:10.1007/BF00589897