Methionine-enkephalin concentrations in discrete brain regions, spinal cord, pituitary gland and peripheral tissues of U-50,488H-tolerant and abstinent rats.
Effects were determined of chronic administration and withdrawal of a highly selective kappa-opioid receptor agonist, U-50,488H, on methionine-enkephalin levels in central and peripheral tissues of male Sprague-Dawley rats. Rats were rendered tolerant to and physically dependent on U-50,488H by twice daily injections of 25 mg/kg of this compound for 5 days. Rats deemed abstinent were injected with this drug for 4 days and sacrificed on 5th day. Methionine-enkephalin concentration increased in the hippocampus of U-50,488H-tolerant-dependent rats, whereas in abstinent rats, its level was elevated only in the hypothalamus. Levels of methionine-enkephalin in the pituitary gland of U-50,488H-tolerant-dependent or abstinent rats were unchanged. Among peripheral tissues, methionine-enkephalin concentration decreased in the adrenal gland of U-50,488H-tolerant-dependent rats. In the U-50,488H-abstinent rats, methionine-enkephalin concentration was elevated in the heart. In tissues of morphine- and U-50,488H-tolerant-dependent and abstinent rats methionine-enkephalin concentrations were affected differentially, suggesting inherent differences in mu- and kappa-opiate-mediated tolerance-dependence and abstinence processes.
Tejwani
G A
GA
Department of Pharmacology, College of Medicine, Ohio State University, Columbus 43210-1239.
Rattan
A K
AK
Koo
K L
KL
Matwyshyn
G A
GA
Bhargava
H N
HN
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology; D004744:Enkephalin, Methionine / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D010902:Pituitary Gland / Q000187:drug effects* / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology*; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D019966:Substance-Related Disorders / Q000378:metabolism
D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D004744:Enkephalin, Methionine; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine