Urethane is a standard anesthetic utilized for in vivo recordings in the hi
ppocampus. In studies of long-term potentiation (LTP), the measure of inter
est is the response amplitude minutes to hours following train delivery. In
the absence of experimental treatment, we have consistently observed upwar
d drift in the amplitude of the population spike (PS) and EPSP slope of the
dentate gyrus (DG) evoked field response in acute surgical preparations pe
rformed in the urethanized rat. The present study systematically monitored
PS amplitude and EPSP slope in the DG every 30 minutes for 6 hours followin
g optimal positioning of Teflon-coated bipolar stainless steel electrodes u
nder urethane anesthesia. At maximal stimulus intensities, large time-depen
dent increases in PS amplitude (70-80%) were observed over the first 2-4 ho
urs, an effect that was exaggerated at lower stimulus intensities. Increase
s in the EPSP slope were smaller in magnitude (20-30%) and stabilized withi
n a shorter period of time (1-2 hours). Animals were warmed on a heating pa
d and body and brain temperature remained constant over the recording sessi
on. Reducing stimulating electrode size and recording with glass micropipet
tes did not alleviate the upward drift in response amplitude. Similar incre
ases were also seen under pentobarbital anesthesia. To dissociate anestheti
c from surgical effects, recordings were obtained from animals previously p
repared with indwelling electrodes and injected with urethane. Although sli
ght declines (10-15%) in EPSP slope occurred over time, no significant alte
rations in PS amplitude were seen in the chronic preparation at high stimul
us intensities. Low stimulus intensities yielded a more variable response p
attern and, in direct contrast to the acute preparation, time-dependent dec
lines, not increases, were noted in both parameters. These data suggest tha
t generalized surgical trauma contributes to the upward drift in response a
mplitude and indicate that long stabilization periods are required in acute
surgical preparations for accurate field potential recordings. Published 1
999 Wiley-Liss, Inc.