Down-regulation of central receptors for thyrotropin-releasing hormone in kappa opiate agonist-induced abstinence in the rat.
The effect of U-50,488H, a selective kappa opiate agonist, on tolerance-dependence and abstinence on the TRH receptors of the spinal cord and discrete regions of the brain of male Sprague-Dawley rats was determined. Rats were injected intraperitoneally twice daily with 25 mg/kg of U-50,488H for 4 days. Rats serving as controls were injected with the vehicle. On day 5, rats which were labeled as tolerant to U-50,488H were injected with U-50,488H (25 mg/kg) and sacrificed 1 hr later, whereas those labeled as abstinent were sacrificed without any injection. The above procedure has been previously shown to produce a high degree of tolerance to the analgesic and hypothermic effects of U-50,488H. The spinal cord and regions of the brain (hippocampus, cortex, midbrain, hypothalamus, corpus striatum, pons and medulla, and amygdala) were isolated for binding studies. The ligand [3H]MeTRH was used for TRH receptors. The binding constants, Bmax and Kd values, of [3H]MeTRH to bind to membranes prepared from various regions of the brain and spinal cord of rats tolerant-dependent on U-50,488H were unaffected. However, in rats abstinent to U-50,488H, the binding of [3H]MeTRH to membranes of the hypothalamus, and pons and medulla, was decreased. The decreased binding of [3H]MeTRH to hypothalamic membranes was due to changes in Bmax value, while in pons and medulla it was due to an increase in the Kd value.(ABSTRACT TRUNCATED AT 250 WORDS)
Bhargava
H N
HN
Department of Pharmacodynamics, University of Illinois, Chicago 60612.
Gulati
A
A
Rahmani
N H
NH
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D015536:Down-Regulation; D004361:Drug Tolerance; D007700:Kinetics; D008297:Male; D009928:Organ Specificity; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000378:metabolism*; D011957:Receptors, Opioid / Q000502:physiology*; D017473:Receptors, Opioid, kappa; D018025:Receptors, Thyrotropin-Releasing Hormone; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013973:Thyrotropin-Releasing Hormone / Q000378:metabolism*
D000700:Analgesics; D011759:Pyrrolidines; D017981:Receptors, Neurotransmitter; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer