Cholinergic mechanisms in startle and prepulse inhibition: effects of the false cholinergic precursor N-aminodeanol

Abstract

We examined the effects of cholinergic deficiency on prepulse inhibition (PPI) of the acoustic startle. Rats treated with a choline-free diet that contained the false cholinergic precursor N-aminodeanol showed great deficit in PPI. This deficit does not appear to be secondary to an increase of stereotyped behaviors. Startle threshold was also greatly reduced, as these rats startled to the 70-dB prepulse and the baseline startle amplitude was increased by 60% over the control rats. Arecoline (4 mg/kg) partially reversed the deficit in PPI. This improvement persisted beyond the period of drug treatment. On the other hand, scopolamine (1 mg/kg) reduced PPI in the control rats. These results suggest that cholinergic systems play a major role in both the elicitation and prepulse inhibition of startle.

Figure 1.

Startle response and prepulse inhibition as a function of elicitation intensity in choline- (control) and N-aminodeanol-treated (experimental) rats. (N-aminodeanol-treated rats showed enhanced startle response [60% and 97% increase over the control rats at 115-dB and 100-dB startle Intensities, respectively] and a deficit in prepulse inhibition [11.9% and 12.5% inhibition with 115-dB and 100-dB startle intensities, respectively] as compared with the control rats [70.7% and 76.2%]. Startle amplitudes in this and other figures represent absolute response size in arbitrary units. C = trials with startle-eliciting stimulus alone: and P = trials with prepulse.)

Figure 2.

Computer averages of startle response (to 115-dB startle-eliciting stimulus) across animals with and without the prepulse in choline- (upper panel) and N-aminodeanol-treated (bottom panel) rats. (N-aminodeanol-treated rats regularly responded to the 70-dB prepulse, in contrast to the control rats, which rarely responded to the prepulse. Time of stimulus presentation is indicated by the arrows. P = prepulse; S = startle-eliciting stimulus.)

Figure 3.

N-aminodeanol-treated (NADe) rats displayed more grooming and stereotyped behaviors than the choline controls in Experiment 1 (Panel A), but the amount of prepulse inhibition was comparable in quiet and active states in Experiment 2 (Panel B). (Data in Panel B are expressed as percentage of the basal startle level during quiet state. Scores in active state represent the averages of all active behavioral states. FW = face washing; GRM = grooming; and SNF = sniffing.)

Figure 4.

Changes (M ± SE) in startle response over trials in N-aminodeanol-treated rats (n = 4). (Each data point is the average of five trials with the stimulus-eliciting stimulus alone and expressed as the percentage of initial startle level. Note that prepulse trials were presented intermixed with trials with startle-eliciting stimulus alone in a total of 150-trial series.)

Figure 5.

Effects of arecoline and scopolamine on the elicitation and prepulse inhibition of the startle response in the choline- (control) and N-aminodeanol-treated rats (top panel), and effects of arecoline on prepulse inhibition of startle in N-aminodeanol-treated rats as a function of order of treatment (bottom panel). (Data represent the percentage reduction from basal startle level. C = trials with startle-eliciting stimulus alone; and P = trials with prepulse.)

Figure 6.

Effects of arecoline and scopolamine on spontaneous activity in the choline- and N-aminodeanol-treated rats.

Figure 7.

Chromatographic analysis of choline and N-aminodeanol (NADe) levels in the cortex, liver, and blood. (Control = choline-treated rats; and Exp. = NADe-treated rats.)