Naltrexone does not affect isoflurane minimum alveolar concentration in cats.

OBJECTIVE: To test whether naltrexone, an opioid receptor antagonist, affects the minimum alveolar concentration (MAC) of isoflurane in cats, a species that is relatively resistant to the general anesthetic sparing effects of most opioids. STUDY DESIGN: Randomized, crossover, placebo-controlled, blinded experimental design. ANIMALS: Six healthy adult cats weighing 4.9 ± 0.7 kg. METHODS: The cats were studied twice. In the first study, baseline isoflurane MAC was measured in duplicate. The drug (saline control or 0.6 mg kg(-1) naltrexone) was administered IV every 40-60 minutes, and isoflurane MAC was re-measured. In the second study, cats received the second drug treatment using identical methods 2 weeks later. RESULTS: Isoflurane MAC was 2.03 ± 0.12% and was unchanged from baseline following saline or naltrexone administration. CONCLUSION AND CLINICAL RELEVANCE: Minimum alveolar concentration was unaffected by naltrexone. Because MAC in cats is unaffected by at least some mu-opioid agonists and antagonists, spinal neurons that are directly modulated by mu-opioid receptors in this species cannot be the neuroanatomic sites responsible for immobility from inhaled anesthetics.

Ketamine exposure in adult mice leads to increased cell death in C3H, DBA2 and FVB inbred mouse strains.

BACKGROUND: Drug abuse is common among adolescents and young adults. Although the consequences of intoxication are known, sequelae of drugs emerging on campuses and in clubs nationwide are not. We previously demonstrated that ketamine exposure results in lasting physiological abnormalities in mice. However, the extent to which these deficits reflect neuropathologic changes is not known. METHODS: The current study examines neuropathologic changes following sub-anesthetic ketamine administration (5mg/kg i.p. x 5) to three inbred mouse strains. Stereologic quantification of silver stained nuclear and linear profiles as well as activated caspase-3 labeling was used to address: (1) whether or not ketamine increases excitotoxic and apoptotic cell death in hippocampal CA3 and (2) whether or not ketamine-induced cell death varies by genetic background. RESULTS: Ketamine increased cell death in hippocampal CA3 of adult C3H, DBA2 and FVB mice. Neither silver staining nor activated caspase-3 labeling varied by strain, nor was there an interaction between ketamine-induced cell death and strain. CONCLUSIONS: Ketamine exposure among young adults, even in limited amounts, may lead to irreversible changes in both brain function and structure. Loss of CA3 hippocampal cells may underlie persistent ERP changes previously shown in mice and possibly contribute to lasting cognitive deficits among ketamine abusers.