Region-specific effects of isoflurane anesthesia on Fos immunoreactivity in response to intravenous cocaine challenge in rats with a history of repeated cocaine administration

• We tested effects of isoflurane anesthesia on cocaine-induced Fos expression.
• Groups of rats had histories of repeated cocaine or saline injections.
• Isoflurane extinguished cocaine-induced Fos in the prefrontal cortex.
• Cocaine-induced Fos was found in nucleus accumbens core, regardless of anesthesia.

We have previously shown that acute intravenous (i.v.) administration of cocaine increases Fos immunoreactivity in rats under isoflurane anesthesia. Given that Fos expression is a marker of neural activation, the results suggested that isoflurane is appropriate for imaging cocaine effects under anesthesia. However, most imaging research in this area utilizes subjects with a history of repeated cocaine exposure and this drug history may interact with anesthetic use differently from acute cocaine exposure. Thus, this study further examined Fos expression under isoflurane in rats with a history of repeated i.v. cocaine administration. Rats received daily injections of either saline or cocaine (2 mg/kg, i.v.) across 7 consecutive days, followed by 5 days of no drug exposure. On the test day, rats were either nonanesthetized or anesthetized under isoflurane and were given an acute challenge of cocaine (2 mg/kg, i.v.). Additional saline-exposed controls received a saline challenge. Ninety min after the drug challenge, the rats were perfused under isoflurane anesthesia and their brains were processed for Fos protein immunohistochemistry. We found that challenge injections of cocaine following a regimen of repeated cocaine exposure resulted in Fos expression in the prefrontal cortex and striatum roughly equivalent to that found in rats who had received the cocaine challenge after a history of vehicle injections. Additionally, isoflurane anesthesia resulted in a heterogeneous attenuation of cocaine-induced Fos expression, with the most robust effect in the orbital cortex but no effect in the nucleus accumbens core (NAcC). These results indicate that cocaine-induced Fos is preserved in the NAcC under isoflurane, suggesting that isoflurane can be used in imaging studies involving cocaine effects in this region.