Brain responses to acute withdrawal in phenobarbital-dependent rats.
Heat shock proteins (HSP) such as HO-1 and HSP27 have been implicated as functioning in a protective manner against oxidative and physical stress. The objective of the current study was to determine the role of HSPs in drug-withdrawal stress induced in phenobarbital-dependent rats. Increased expression of HO-1 and HSP27 was observed in the hippocampus and the cerebral cortex of phenobarbital-withdrawn rats. Gene expression was measured by Northern and Western blot analyses and in situ hybridization. The induction of HO-1 mRNA was suppressed by the administration of the NMDA receptor antagonist, (+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d) cyclohepten-5,10-imine (MK801). Despite significant upregulation of glutamatergic transmission, neuronal cell degeneration was not apparent. These findings suggest that the induction of HO-1 and HSP27 during withdrawal from phenobarbital dependence may play a role in protection against glutamate toxicity.
Tanaka
S
S
Department of Biochemical Toxicology, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa, Tokyo, 142-8555, Japan. stanaka@pharm.showa-u.ac.jp
Okuno
Y
Y
Numazawa
S
S
Yamamoto
T
T
Shioda
S
S
Yoshida
T
T
D000818:Animals; D000927:Anticonvulsants / Q000009:adverse effects*; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D051547:Heme Oxygenase-1; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017403:In Situ Hybridization; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010634:Phenobarbital / Q000009:adverse effects*; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000502:physiology; D013375:Substance Withdrawal Syndrome / Q000378:metabolism; D019966:Substance-Related Disorders
D000927:Anticonvulsants; D018691:Excitatory Amino Acid Antagonists; D055551:HSP27 Heat-Shock Proteins; D006360:Heat-Shock Proteins; C486114:Hspb1 protein, rat; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D010634:Phenobarbital