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Abstract

Behavioral effects of opioid peptides selective for mu or delta receptors. I. Morphine-like discriminative stimulus effects.

K W Locke and S G Holtzman
Journal of Pharmacology and Experimental Therapeutics September 1986, 238 (3) 990-996;
K W Locke
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S G Holtzman
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Abstract

The morphine-like discriminative stimulus effects of opioid peptides with selectivity for the mu- or delta-opioid receptors were examined in rats trained to discriminate 3.0 mg/kg of morphine (s.c.) from saline in a two-choice discrete-trial avoidance paradigm. The mu-selective peptides D-Ala2-NMePhe4-Gly5(ol)enkephalin, FK 33,824 and morphiceptin, the delta-selective peptides D-Ala2-D-Leu5enkephalin and metkephamid and beta-endorphin (mu- and delta-selective) produced morphine-like stimulus effects after administration into the lateral ventricle. Generalization with the morphine cue was dose-dependent and occurred over a wide range of doses (0.01-30 micrograms), depending upon peptide. On a molar basis, the order of relative potency of the peptides as morphine-like discriminative stimuli was: D-Ala2-NMePhe4-Gly5(ol)enkephalin = FK 33,824 greater than beta-endorphin greater than D-Ala2-D-Leu5enkephalin = metkephamid greater than morphiceptin. The discriminative effects of D-Ala2-NMePhe4-Gly5(ol)enkephalin, D-Ala2-D-Leu5enkephalin and beta-endorphin were antagonized by low doses of s.c. naltrexone (0.01-1.0 mg/kg). Furthermore, the stimulus effects of s.c. morphine were antagonized by 24-hr pretreatment of rats with the irreversible mu-antagonist beta-funaltrexamine (5.0 micrograms i.c.v.). Based upon the order of relative potency of the peptides and the relative potency for antagonism of their discriminative effects by naltrexone and beta-funaltrexamine, mu-opioid receptors in the brain appear to be an important element in the genesis of morphine-like discriminative effects by opioid peptides.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 238, Issue 3
1 Sep 1986
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Abstract

Behavioral effects of opioid peptides selective for mu or delta receptors. I. Morphine-like discriminative stimulus effects.

K W Locke and S G Holtzman
Journal of Pharmacology and Experimental Therapeutics September 1, 1986, 238 (3) 990-996;

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Abstract

Behavioral effects of opioid peptides selective for mu or delta receptors. I. Morphine-like discriminative stimulus effects.

K W Locke and S G Holtzman
Journal of Pharmacology and Experimental Therapeutics September 1, 1986, 238 (3) 990-996;
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