Effects of Peptidase Inhibitors, jp-Ala2, Met5]-Enkephalinamide and Antiserum to Methionine-Enkephalin Microinjected Into the Caudal Periaqueductal Gray on Morphine Withdrawal in Rats

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Abstract

We examined the involvement of enkephalins in the caudal periaqueductal gray (cPAG) in morphine withdrawal in rats. Rats were treated with increasing doses of morphine (20 - 30 mg/kg/day, s.c., for 5 days) to develop morphine dependence. Morphine withdrawal was induced by naloxone (5 mg/kg, s.c.) 24 hr after the final morphine injection. The level of preproenkephalin (PPE) mRNA in the cPAG was estimated by quantitative <I>in situ</I> hybridization. PPE mRNA in the cPAG was increased 4 - 24 hr after naloxone in morphine-treated rats. A mixture of peptidase inhibitors (0.5 μl of a solution of amastatin, captopril and phosphoramidon, 3×10<SUP>-3</SUP> M each) microinjected into the cPAG suppressed morphine withdrawal (a decrease in the number of jumping, chin rubbing, paw rubbing and teeth chattering). Antiserum to methionine-enkephalin (1:10 dilution) microinjected into the cPAG did not significantly aggravate morphine withdrawal with or without the mixture of peptidase inhibitors. However, [D-Ala<SUP>2</SUP>, Met<SUP>5</SUP>]-enkephalinamide (20 nmol), an enkephalin analog, injected into the cPAG decreased the number of jumping without any influence on the other withdrawal signs. These results suggest that the increase in enkephalins in the cPAG may participate in the alleviation of morphine withdrawal ( jumping behavior).

Journal

  • The Japanese Journal of Pharmacology

    The Japanese Journal of Pharmacology 78(4), 455-461, 1998-12-01

    The Japanese Pharmacological Society

References:  33

Cited by:  1

Codes

  • NII Article ID (NAID)
    10008681746
  • NII NACSIS-CAT ID (NCID)
    AA00691188
  • Text Lang
    ENG
  • Article Type
    Journal Article
  • ISSN
    00215198
  • NDL Article ID
    4629550
  • NDL Source Classification
    ZS51(科学技術--薬学)
  • NDL Call No.
    Z53-D199
  • Data Source
    CJP  CJPref  NDL  J-STAGE 
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