SELECTIVE EFFECTS OF PENTOBARBITAL AND HALOTHANE ON C-FOS AND JUN-B GENE-EXPRESSION IN RAT-BRAIN

The effects of pentobarbital and halothane anesthesia on the expression in brain of the immediate-early genes c-fos and jun-B were investigated. Pentobarbital-anesthetized rats (n = 10) received a single intraperitoneal injection of pentobarbital 65 mg/kg in a vehicle of 40% propylene glycol and 10% ethanol and then were placed in a plexiglass box flushed continuously with 100% oxygen at 5 l/min. Halothane-anesthetized rats (n = 10) received an intraperitoneal injection of vehicle only and were transferred to a box flushed continuously with oxygen plus 1.5% halothane. Unanesthetized control rats (n = 10) received an intraperitoneal injection of vehicle and were placed in a box flushed continuously with 100% oxygen. Four additional rats received no intraperitoneal injection but were handled and otherwise treated identically to the control group, and six others had a femoral arterial catheter inserted for blood pressure and blood gas measurements. Five animals from the control and both anesthetized groups were killed at 30 and 120 min postinjection and their brains rapidly removed and frozen. The messenger ribonucleic acid transcription products of the genes c-fos, jun-B, and beta-actin from whole cerebral hemispheres were analyzed autoradiographically after Northern blot hybridization with P-32-labeled deoxyribonucleic acid probes. Relative levels of c-fos and jun-B messenger ribonucleic acid were determined from optical density measurements of the autoradiographic bands, with beta-actin measurements being used to correct for sample-to-sample variation. Rats became immobile within minutes of drug administration and remained anesthetized until they were killed. The anesthetics had little effect on mean arterial blood pressure, rectal temperature, and Pa(O2); however, pentobarbital-anesthetized rats were hypercarbic at both 30 and 120 min. Because halothane also produced hypercarbia at 120 min, there were no physiologic differences between anesthetics at this later point. Handling of rats did not change c-fos or jun-B expression. Intraperitoneal injection produced a 2- to 3-fold increase i n the whole brain levels of c-fos and jun-B messenger ribonucleic acid (P < 0.01 for all comparisons) at 30 min versus 120 min. Neither anesthetic modified this increase in c-fos and jun-B expression at 30 min postinjection. At 120 min postinjection, selective anesthetic effects were apparent. Jun-B expression was 25% greater than that of control in pentobarbital-anesthetized rats (P < 0.05) and 38% lower in halothane-anesthetized rats (P < 0.01), but neither anesthetic affected c-fos expression. Because immediate-early genes are thought to play a pivotal role in neural mechanisms of stress, memory, and pain/analgesia, anesthetic-induced changes in jun-B expression may pertain to modifications that occur in these biological processes during the anesthetic state. In a broader sense, these data indicate that general anesthetics selectively alter expression of genes in the central nervous system.