Changes in [3H]forskolin binding to adenylate cyclase and [3H]phorbol dibutyrate binding to protein kinase C in pentobarbital tolerant/dependent rats

These studies were designed to examine the effect of chronic administration of pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in the rat brain by autoradiography. Recently, it has been suggested that the phosphorylation of specific proteins may be involved in the deve...

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Bibliographic Details
Published in:Neurochemical research 1998-04, Vol.23 (4), p.463-467
Main Authors: SEIKWAN OH, WELLMAN, S. E, HO, I. K
Format: Article
Language:English
Subjects:
Adenylyl Cyclases - metabolism
Anesthetics. Neuromuscular blocking agents
Animals
Biological and medical sciences
Brain - enzymology
Cerebral Ventricles - drug effects
Cerebral Ventricles - physiology
Colforsin - metabolism
Drug Tolerance
Infusions, Parenteral
Kinases
Male
Medical sciences
Neuropharmacology
Organ Specificity
Pentobarbital - administration & dosage
Pentobarbital - pharmacology
Pharmacology. Drug treatments
Phorbol 12,13-Dibutyrate - metabolism
Protein Binding
Protein Kinase C - metabolism
Proteins
Rats
Rats, Sprague-Dawley
Rodents
Substance Withdrawal Syndrome - metabolism
Substance-Related Disorders - enzymology
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Summary:These studies were designed to examine the effect of chronic administration of pentobarbital on activity of adenylate cyclase (AC) and protein kinase C (PKC) in the rat brain by autoradiography. Recently, it has been suggested that the phosphorylation of specific proteins may be involved in the development of physical dependence. An experimental model of barbiturate tolerance and dependence was developed using i.c.v. infusion of pentobarbital (300 microg/10 microl/hr for 7 days) by osmotic minipumps and abrupt withdrawal from pentobarbital. The levels of [3H]forskolin binding were elevated (28-67%) in cortex, thalamus, dentate gyrus, hippocampal CA3 and cerebellum of the pentobarbital withdrawal animals, while these changes were not observed in tolerant rats. The levels of [3H]phorbol dibutyrate binding were highly elevated (38-65%) in the region of cortex, caudate putamen, septum, thalamus, dentate gyrus, and cerebellum of rats withdrawal from pentobarbital. These results show that the levels of AC and PKC were significantly elevated in pentobarbital withdrawal rats, and suggest that the levels of AC and PKC are altered in a region-specific manner during pentobarbital withdrawal.
ISSN:0364-3190
1573-6903
DOI:10.1023/A:1022466114658