Delayed Development of Fear-Potentiated Startle in Rats
Copyright 1994 by the American Psychological Association, Inc.
Behavioral Neuroscience
0735-7044/94/S3.00
1994, Vol. 108, No. 1,69-80
http://ishare.iask.sina.com.cn/f/33945368.html
Pamela S. Hunt, Rick Richardson, and Byron A. Campbell
Pamela S. Hunt, Rick Richardson, and Byron A. Campbell, Department of Psychology, Princeton University.
This research was supported by National Institute of Mental Health Grants MH01562 and MH49496 to Byron A. Campbell and National Institutes of Child Health and Human Development Postdoctoral Grant HD07694 to Pamela S. Hunt.
Correspondence concerning this article should be addressed to Pamela S. Hunt, Department of Psychology, Princeton University, Green Hall, Princeton, New Jersey 08544-1010. Electronic mail may be sent to pshunt@pucc.princeton.edu.
The developmental emergence of fear-potentiated startle was examined in rats ranging in age from 16 to 75 days. In Experiment 1, a pure tone served as the conditioned stimulus (CS) and an acoustic startle pulse served as the unconditioned stimulus (US) for fear conditioning. Fear-potentiated startle by the tone CS was observed in rats 23 days of age and older but not in rats 16 days of age. In Experiment 2, a light served as the CS. Rats 30 days of age and older showed fear-potentiated startle, whereas 23-day-old rats did not. The final experiment demonstrated that another behavioral index of fear, stimulus-elicited freezing, was observed earlier in development than fear-potentiated startle, confirming the effectiveness of the training procedure for conditioning fear. The results suggest that fear-potentiated startle is a relatively late-emerging response system, parallelling the development of conditioned autonomic changes (e.g., heart rate) rather than that of freezing.
Fear-potentiated startle is a commonly used measure of fear conditioning (Brown, Kalish, & Farber, 1951; Davis & Astrachan, 1978; Hamm, Greenwald, Bradley, Cuthbert, & Lang, 1991; Lang, Bradley, & Cuthbert, 1990; Leaton & Borszcz, 1985). For example, when rats are presented with a startle-eliciting stimulus, typically a brief, intense auditory stimulus, they respond behaviorally with a whole-body jerk, referred to as the startle reflex. When the startle stimulus is preceded by a cue that evokes fear, such as a light that has been paired with shock, the startle response is greater than when the startle stimulus is presented alone. This enhancement in startle responding is termed fear-potentiated startle, and it has been extensively used as a tool for examining the pharmacological and neuroanatomical bases of conditioned fear (Cassella & Davis, 1985; Davis, 1979, 1984, 1986, 1992a, 1992b; Davis, Hitchcock, & Rosen, 1992; Hitchcock & Davis, 1986, 1987, 1991; Rosen & Davis, 1988; Sananes & Davis, 1992). The purpose of the following experiments was to investigate the emergence of fear-potentiated startle during development, using auditory and visual stimuli as conditioned stimuli (CSs).
Two disparate lines of evidence converge to make the ontogenetic study of fear-potentiated startle particularly interesting. First, Wecker and Ison (1986) showed that the magnitude of the startle response is highly correlated with the type of behavior occurring just prior to the elicitation of startle. In their study, adult rats were shown to exhibit a greater startle response when they were immobile prior to the presentation of a startle-eliciting noise burst than when they were active. The reduction in startle response magnitude during activity was particularly marked when the animals were engaged in consum-ing (eating or drinking), grooming, or sniffing behavior. This relation between activity and startle response magnitude has also been implicated in fear-potentiated startle. According to Leaton and Borszcz (1985), a CS that has been paired with an aversive stimulus elicits the species-specific response of freezing in the laboratory rat and that when that CS precedes a startle stimulus, the resulting immobility potentiates the startle response (see also Leaton & Cranney, 1990).
Although we could find no research on the correspondence between freezing and startle responding during development, several researchers have demonstrated that infant, as well as adult, rats show a decrease in activity in the presence of a CS that has been paired with shock (Campbell & Ampuero, 1985; Coulter, Collier, & Campbell, 1976; Mellon, Kraemer, & Spear, 1991; Moye & Rudy, 1985, 1987). For example, Moye and Rudy (1987) paired a tone CS with shock for preweanlings rats of different ages; when the tone was presented 24 hr later, it produced a substantial decrease in general activity in rats 15 days of age and older. It is a reasonable prediction then that animals as young as 15-16 days of age would show the potentiated startle effect given their disposition to respond with inactivity (freezing) to a tone that had been paired with shock.
A second line of evidence, however, suggests that potentiated startle may not be observed until much later in development. A number of investigators, working with other species such as the rabbit and cat, have shown that reflex sensitivity is altered by stimulation of the amygdala, particularly the central nucleus, from which concomitant changes in heart rate (HR) are also evoked. Whalen and Kapp (1991) reported that the amplitude of the rabbit's nictitating membrane reflex (NMR) was enhanced by stimulation of the central nucleus of the amygdala that also evoked bradycardia but that it was inhibited by stimulation of other regions of the amygdala that concomitantly evoked tachycardia. From these results, Whalen and Kapp (1991) proposed that heart rate change and reflex modification covaried, with heart rate decreases accompanying facilitation and heart rate increases accompanying inhibition of the magnitude of the response (see also Gary Bobo & Bonvallet, 1975; Gebber & Klevans, 1972; Kapp, Whalen, Supple, & Pascoe, 1992; Marks, Frysinger, Trelease, & Harper, 1983; Pascoe, Bradley, & Spyer, 1989; Schlor, Stumpf, & Stock, 1984). Although none of these researchers explicitly postulated a causal relation between HR changes and alterations in reflex amplitude, the findings that the two measures occur together suggest that they are somehow related.
Conditioned changes in HR have been documented in young rats when auditory and visual stimuli are paired with an aversive stimulus such as shock (Campbell & Ampuero, 1985) or a startle pulse (Richardson, Wang, & Campbell, 1993). However, conditioned heart rate responses emerge much later in development than behavioral measures of fear such as freezing or conditioned suppression of locomotion. Specifically, although there are numerous demonstrations of stimulus-elicited freezing to auditory and visual CSs as early as 15-17 days postnatal (Campbell & Ampuero, 1985; Coulter et al., 1976; Mellon et al., 1991; Moye & Rudy, 1985, 1987), conditioned changes in heart rate to auditory and visual stimuli are not observed until approximately 21 and 28 days of age, respectively (Campbell & Ampuero, 1985). Thus, if facilitation of the startle reflex is correlated with stimulus-elicited changes in heart rate (in this case attributable to conditioning), potentiated startle would not be expected to occur until about 21 days of age to auditory stimuli that had previously been paired with shock and not until 28 days of age to visual stimuli. These two lines of evidence lead to quite different predictions concerning the age at which fear-potentiated startle should first emerge during the course of development. If it is conditioned immobility (freezing) that is associated with enhanced startle magnitude, then fear-potentiated startle to auditory stimuli should emerge about 15 days of age and around 17 days of age to visual stimuli. Conversely, if conditioned changes in heart rate are critical predictors of startle modulation, then fear-potentiated startle should not be observed until approximately 21 and 28 days of age to auditory and visual stimuli, respectively.
Experiments 1A and IB