Isoflurane anesthesia interferes with the expression of cocaine-induced sensitization in female rats

Repeated cocaine administration results in a progressive sensitization of behavior which typically occurs more readily in female rats than in males. Our recent studies of rats undergoing surgical procedures revealed that following anesthesia, females sensitized less than males receiving identical repeated cocaine injections. Since isoflurane acts primarily by increasing the effects of the inhibitory neurotransmitter γ-amino butyric acid (GABA) and reducing the effects of the excitatory amino acid glutamate, these amino acids may play more prominent roles in sensitization to cocaine in females than previously understood. In order to examine the effects of isoflurane on cocaine-sensitization, we administered cocaine (15 mg/kg i.p) or saline to adult male and female Sprague-Dawley rats for 9 days; on day 10, half of the rats were subjected to isoflurane anesthesia and the other half did not receive anesthesia. On day 11, rats were given their last dose of either cocaine or saline. We recorded behaviors for 1 h on days 1, 9 and 11. Locomotor activity and stereotyped behaviors were quantified using photo beam monitors and the scoring of video tapes, respectively. Results indicated that a single exposure to isoflurane significantly dampens the stereotypic behavior associated with repeated cocaine administration in females but not in males. They further suggest that either GABA or glutamate play more prominent roles in cocaine-sensitization behavior in females than in males.