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 Increased expression of HO-1 and HSP27 was observed in the hippocampus and the cerebral cortex of phenobarbital-withdrawn rats.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.