The effect of U-50,488H tolerance-dependence and abstinence on the levels of dynorphin (1-13) in brain regions, spinal cord, pituitary gland and peripheral tissues of the rat.
Male Sprague-Dawley rats were rendered tolerant to and physically dependent on U-50,488H, a kappa-opiate agonist, by injecting 25 mg/kg of the drug intraperitoneally twice a day for 4 days. Two sets of rats were used. Rats labeled as tolerant-dependent were injected with U-50,488H (25 mg/kg) 1 h before sacrificing on day 5, whereas the abstinent rats were sacrificed on day 5 without the injection of U-50,488H. Of all the tissues on day 5 without the injection of U-50,488H. Of all the tissues examined, the pituitary gland had the highest level of dynorphin (1-13), whereas the heart had the lowest level. The levels of dynorphin (1-13) increased in the hypothalamus, hippocampus and pons/medulla of U-50,488H tolerant-dependent rats, whereas in abstinent rats the levels of dynorphin (1-13) were elevated only in the midbrain. The levels of dynorphin (1-13) in the pituitary gland of U-50,488H tolerant-dependent or abstinent rats were unchanged. In peripheral tissues, the levels of dynorphin (1-13) in the heart of U-50,488H tolerant-dependent rats were increased. In the abstinent rats they were elevated in the adrenals, spleen, and the heart but were decreased in the kidneys. Compared to morphine tolerant-dependent and abstinent rats, significant differences in the levels of dynorphin (1-13) in tissues of 50,488H tolerant-dependent and abstinent rats were observed and may explain many pharmacological differences in the mu- and kappa-opiate induced tolerance-dependence and abstinence processes.
Bhargava
H N
HN
Department of Pharmacodynamics (m/c 865), University of Illinois, Chicago 60612.
Matwyshyn
G A
GA
Rattan
A K
AK
Koo
K L
KL
Tejwani
G A
GA
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D004361:Drug Tolerance; D004399:Dynorphins / Q000378:metabolism*; D006321:Heart / Q000187:drug effects; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010446:Peptide Fragments / Q000378:metabolism*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*; D019966:Substance-Related Disorders
D000700:Analgesics; D010446:Peptide Fragments; D011759:Pyrrolidines; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C026843:dynorphin (1-13); D004399:Dynorphins