Animals and treatments

Pregnant Sprague-Dawley rats were purchased; 80 offspring were used in these experiments with the approval of the local Animal Care and Use Committee. Pups were divided into 2 arms (arm A and B; Female/male=1:1). Pups in arm A (n=50) were raised for behavioral tests on postnatal day (P) 41. Pups in arm (n=30) B were sacrificed at P41 to evaluate the effects of anesthesia on neurogenesis. The experimental design and groups are shown in Figure 1. Pups in arms A and B were divided into 5 treatment groups. During postnatal weeks 1–2, a combination of subcutaneous (SC) ketamine 25 mg/kg (10 mg/mL) plus intraperitoneal (IP) propofol 10 mg/kg (10 mg/mL) were administered on P7 (Single Ketamine Propofol: SKP) or 3 administrations on P6, P8, and P10 (Multiple Ketamine Propofol: MKP). Pups in group C (Control) received equivalent volumes of normal saline in 3 injections on P6, P8, and P10. Ketamine was administered 5–10 min prior to the administration of propofol. Animals were observed for 90 min until they were awake and active, at which time they were returned to their mother. Pups remained with their mother until weaning on P21. All rats were kept in plastic cages at 22±0.5°C and 40% to 70% humidity with a 12 h light/dark cycle and ad libitum access to food and water.

Experimental design. Three hypotheses were tested. (1) Multiple versus single exposure to propofol + ketamine will increase functional deficits in adult rats. (2) Running exercise can improve intravenous anesthesia-related learning and memory impairment. (3) Anesthesia-induced memory impairment will be improved by running exercise and alter hippocampal neurogenesis. P – postnatal day. SKP – single ketamine + propofol administration; MKP – multiple ketamine + propofol administrations; C – saline + saline, 3 times; MKPR – MKP plus running exercise; CR – C plus running exercise.