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OtherNEUROPHARMACOLOGY

Opioid Regulation of Pallidal Enkephalin Release: Bimodal Effects of Locally Administered Mu and DeltaOpioid Agonists in Freely Moving Rats

M. Foster Olive and Nigel T. Maidment
Journal of Pharmacology and Experimental Therapeutics June 1998, 285 (3) 1310-1316;
M. Foster Olive
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Nigel T. Maidment
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Abstract

The globus pallidus and ventral pallidum receive dense enkephalinergic innervation from the dorsal and ventral striatum, respectively. A previous study demonstrated peripheral morphine administration to increase pallidal enkephalin release. To determine whether such opioid stimulatory effects may be mediated directly in the pallidum, in vivo microdialysis was used to study the effects of local administration of several concentrations of themu receptor agonists morphine and morphine-6-glucuronide (M6G) as well as the the delta receptor agonist SNC80 on pallidal enkephalin release in freely moving rats. Low concentrations of morphine or M6G (1–10 nM) enhanced the release of enkephalins, an effect that was reversed by coadministration of the mureceptor antagonist β-funaltrexamine (β-FNA). A similar stimulatory effect was observed with a low concentration of SNC80 (50 nM), an effect that was blocked by the delta antagonist naltrindole (NTD). High concentrations of morphine (100 nM to 100 μM) had little or no effect, whereas M6G (10 μM) suppressed enkephalin release, an effect that was reversed by β-FNA. Similarly, a high concentration (5 μM) of SNC80 suppressed enkephalin release. However, this effect was not blocked by NTD but was attenuated by β-FNA, suggesting a mu receptor-mediated action. These results offer in vivo evidence of bimodal (i.e., stimulatory and inhibitory) effects of mu and delta opioid agonists on enkephalin release in the pallidum.

Footnotes

  • Send reprint requests to: Nigel T. Maidment, Ph.D., Department of Psychiatry and Biobehavioral Sciences, UCLA-NPI, 760 Westwood Plaza, Los Angeles, CA 90024-1759. E-mail: nmaidmen{at}ucla.edu

  • ↵1 This study was supported by United States Public Health Sevice Grants DA05010 and DA09359. M.F.O. was supported by NRSA Predoctoral Fellowship from the National Institute on Drug Abuse (Grant DA05634) and by a Hatos Scholarship.

  • Abbreviations:
    aCSF
    artificial cerebrospinal fluid
    ANOVA
    analysis of variance
    AP
    anterior-posterior
    β-FNA
    β-funaltrexamine
    DAMGO
    [d-Ala2,N-Me-Phe4,Gly-ol]enkephalin
    GP
    globus pallidus
    VP
    ventral pallidum
    DPDPE
    [d-Pen2,5]enkephalin
    DV
    dorsal-ventral
    ENK
    enkephalin
    HPLC
    high performance liquid chromatography
    M6G
    morphine-6-glucuronide
    ML
    medial-lateral
    NTD
    naltrindole
    SNC80
    (+)-4-[(αR)-α-[(2S,5R)-4-allyl-2,5-dimethyl-1-piperazinyl]-3-methoxybenzyl]-N,N-diethylbenzamide
    • Received September 24, 1997.
    • Accepted February 16, 1998.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 3
1 Jun 1998
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OtherNEUROPHARMACOLOGY

Opioid Regulation of Pallidal Enkephalin Release: Bimodal Effects of Locally Administered Mu and DeltaOpioid Agonists in Freely Moving Rats

M. Foster Olive and Nigel T. Maidment
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1310-1316;

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OtherNEUROPHARMACOLOGY

Opioid Regulation of Pallidal Enkephalin Release: Bimodal Effects of Locally Administered Mu and DeltaOpioid Agonists in Freely Moving Rats

M. Foster Olive and Nigel T. Maidment
Journal of Pharmacology and Experimental Therapeutics June 1, 1998, 285 (3) 1310-1316;
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