Effects of ketamine anesthesia on the rat brain-stem auditory evoked potential as a function of dose and stimulus intensity

Because ketamine is both an abused substance and a commonly used veterinary anesthetic, its effects on brain and sensory functions are of interest. The present study examined the dose-dependent effects of ketamine anesthesia in the rat, using the brain-stem auditory evoked potential (BAEP) as an objective, quantitative measure of this substance's acute effects on brain and sensory electrophysiology. The animal subjects were 11 young adult female Long-Evans rats. BAEPs were recorded from skull screw electrodes during a baseline period as well as after saline and ketamine treatments. Ketamine was administered (i.p.) in 2 serial doses. The first dose (100 mg/kg) was followed 30-40 min later by a second dose (also 100 mg/kg). Equal volumes of normal saline were also injected serially. An interval of 1-2 weeks occurred between the saline and ketamine treatments, with treatment order counterbalanced. Normothermia was maintained to control for possible temperature-related effects. Ketamine produced prolongations in the latencies of all BAEP components (P1 through P6) that were statistically significant relative to baseline values. These latency shifts were progressively greater for waves P1 through P4 (shifts in P5 and P6 approximated the P4 shift). The effect of the second ketamine injection was to nearly double the latency shifts. Ketamine also had significant and complex effects on BAEP amplitudes that were dependent on dose and stimulus intensity. The results of the present study challenge the belief that the BAEP is resistant to the effects of anesthetics and suggest that the BAEP is useful in characterizing the CNS and sensory effects of these pharmacological agents.