Table 5.
VsEP amplitudes and thresholds in diazepam and BPEW vehicle progressive multiple dose (PMD) protocol with and without brain temperature controlled. VsEP amplitudes (µV) at + 6 dB re: 1.0 g/ms and thresholds were obtained over a period of 80 min following a 20-min stable baseline period. Data were obtained from mice where brain and rectal temperatures were controlled (“Brain + Rectal”) as well as from mice where only rectal temperature was controlled (”Rectal Only”). Four incremental doses of diazepam were given (post dose 1 “PD1”: 6 mg/kg; post dose 2 “PD2”: 12 mg/kg; post dose3 “PD3”: 24 mg/kg; post dose 4 “PD4”: 48 mg/kg). Each time period (20 min) was characterized by averaging 4 to 5 consecutive 5-min measurements. Data reflect mean ± standard deviation. “Rectal only” animals were anesthetized with ketamine/xylazine whereas “Brain + Rectal” animals were anesthetized with urethane/xylazine. Brain temperatures were held at 36.0 ± 0.2 °C and rectal at 37.0 ± 0.2 °C. BPEW vehicle: 1.4% benzyl alcohol, 38.5% propylene glycol, 12.7% ethyl alcohol and 48% water. In the “Injection” column, the parentheses “(n)” reflect the sample size, which remained constant over the entire study
| VsEP parameters | Temperatures | Injection (n) | Baseline | PD1 (1–20 min) | PD2 (21–40 min) | PD3 (41–60 min) | PD4 (61–80 min) | |
|---|---|---|---|---|---|---|---|---|
| Amplitude (µV) | P1-N1 | Brain + Rectal | Diazepam (10) | 0.92 ± 0.21 | 0.95 ± 0.22 | 0.89 ± 0.27 | 0.92 ± 0.20 | 0.95 ± 0.20 |
| BPEW (6) | 0.91 ± 0.11 | 0.96 ± 0.11 | 1.00 ± 0.13 | 0.96 ± 0.15 | 0.97 ± 0.14 | |||
| Rectal Only | Diazepam (10) | 1.03 ± 0.30 | 1.00 ± 0.32 | 0.97 ± 0.31 | 1.03 ± 0.28 | 1.00 ± 0.32 | ||
| BPEW (10) | 1.13 ± 0.29 | 1.10 ± 0.24 | 1.09 ± 0.28 | 1.07 ± 0.29 | 1.04 ± 0.30 | |||
| P2-N1 | Brain + Rectal | Diazepam (10) | 0.93 ± 0.21 | 0.99 ± 0.23 | 1.02 ± 0.23 | 0.97 ± 0.21 | 1.06 ± 0.25 | |
| BPEW (6) | 0.98 ± 0.34 | 1.03 ± 0.39 | 1.03 ± 0.36 | 1.07 ± 0.30 | 1.08 ± 0.34 | |||
| Rectal Only | Diazepam (10) | 1.12 ± 0.28 | 1.08 ± 0.32 | 1.06 ± 0.31 | 1.13 ± 0.32 | 1.07 ± 0.30 | ||
| BPEW (10) | 1.20 ± 0.32 | 1.17 ± 0.36 | 1.08 ± 0.32 | 1.08 ± 0.33 | 1.11 ± 0.32 | |||
| Threshold (dB re: 1.0 g/ms) | Brain + Rectal | Diazepam (10) | − 13.5 ± 1.4 | − 12.0 ± 1.6 | − 11.4 ± 1.5 | − 11.1 ± 1.9 | − 11.4 ± 1.4 | |
| BPEW (6) | − 10.0 ± 1.2 | − 10.0 ± 1.2 | − 9.5 ± 2.5 | − 9.5 ± 1.6 | − 10.0 ± 1.2 | |||
| Rectal Only | Diazepam (10) | − 12.6 ± 2.0 | − 11.1 ± 1.9 | − 11.1 ± 2.8 | − 10.5 ± 2.5 | − 9.6 ± 1.4 | ||
| BPEW (10) | − 11.7 ± 2.1 | − 11.1 ± 1.3 | − 11.4 ± 2.0 | − 11.4 ± 2.0 | − 11.7 ± 1.5 | |||