Fear reduction in the rat following central cholinergic blockade.

In the presence of a natural predator, cat, 92 male Long-Evans hooded rats (in 2 experiments) showed a constellation of responses that was used to define fear: freezing, avoiding the cat, and suppressing consummatory behavior. Compared with controls, Ss treated with an anticholinergic drug, scopolamine, showed significantly less freezing and significantly more approach to the cat; further, these Ss actually engaged in consummatory behavior in proximity to the cat. On a 2nd, undrugged exposure to the cat, the original scopolamine-treated Ss continued to show significantly less freezing, more approach, and more drinking than control Ss. Since methyl scopolamine, which mimics the peripheral actions of scopolamine, had no effect on fear responses, these results implicate a central cholinergic system in fear responses or species-typical defense reactions. (24 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Both pre- and posttraining excitotoxic lesions of the basolateral amygdala abolish the expression of olfactory and contextual fear conditioning

The present study examined whether the basolateral amygdaloid complex (BLA) participates in the expression of fear conditioned to both an olfactory conditioned stimulus (CS) and the training context. In Experiment 1, pretraining excitotoxic lesions of the BLA abolished immediate postshock freezing, conditioned freezing to an olfactory CS, and conditioned freezing to the training context. Control experiments indicated that lesioned and sham-lesioned subjects did not differ in locomotor activity or in acquisition of a successive-cue odor discrimination task, suggesting that deficits in freezing behavior exhibited by BLA subjects were not due to an impairment in primary aspects of olfaction or to a general enhancement of locomotor activity. In Experiment 2, excitotoxic lesions of the BLA produced either 1 day or 15 days after olfactory fear conditioning abolished both odor-elicited and contextual freezing. Collectively, these data support the notion that the BLA participates in an enduring manner in the expression of conditioned freezing behavior elicited by both olfactory and contextual stimuli.     

The ontogeny of conditioned odor potentiation of startle.

During development, conditioned responses usually occur first to olfactory, then to auditory, and finally to visual cues. The authors of the present study report that fear potentiation of startle to an olfactory conditioned stimulus emerges relatively late in development (i.e., at 23 days of age; Experiments 1 and 2). The failure to observe conditioned odor potentiation of startle (OPS) in younger rats was not due to a failure to either acquire or remember the odor-shock association (Experiment 3). Surprisingly, the authors also found that rats trained at 16 but tested at 23 days of age failed to exhibit the OPS effect even though they did exhibit pronounced odor avoidance (Experiment 4). The results are discussed in terms of (a) sensory-specific sequential emergence of learned fear, (b) the neural circuit involved in fear potentiation of startle, and (c) the concept that conditioned responding is appropriate to the animal's age at the time of training rather than its age at testing. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Stimulus control of defensive reactions in the albino rat.

Conducted 4 experiments with a total of 132 male Wistar rats to examine the characteristics of stimuli that produce unconditioned defensive reactions. Results show that neither the sound nor the smell of a cat, or the sight of a dead cat, produced freezing, but that either a moving cat or dog, or the abrupt and rapid movement of an inanimate card, resulted in freezing and failure to approach the stimulus object. It is suggested that movement is a major factor in the initiation of defensive responses and that movement of a neutral stimulus may enhance the acquisition of defensive responses to that stimulus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of hippocampal lesions on the rat's reaction to a cat.

Confronted 20 male albino rats with a cat in a circular runway. Ss with hippocampal lesions displayed lower levels of freezing than did operated controls. When avoidance or escape was possible, Ss with lesions showed superior cat avoidance and less freezing in the intervals between cat approaches. The similarity of reactions to a cat and to conditioned threat stimuli in Ss with hippocampal damage suggests that the effects of hippocampal damage in aversive conditioning tasks may be largely mediated by an alteration of innate freezing reactions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of lesions to the hippocampus on contextual fear: Evidence for a disruption of freezing and avoidance behavior but not context conditioning.

The effects of ibotenic lesions of the hippocampus on conditioning to contextual cues during classical fear conditioning in rats were evaluated by (a) the amount of freezing elicited by contextual cues and (b) the relative avoidance of a shock compartment. In Experiment 1, lesions to the hippocampus had no effect on contextual freezing and marginally affected avoidance after repeated sessions. Experiment 2 showed that lesions to the hippocampus disrupted avoidance when tested after a single conditioning session, while leaving unaffected the acquisition of contextual freezing. Experiment 3 indicated that these lesions decreased the acquisition of contextual freezing when higher footshock intensity was used but had no effect on avoidance after repeated conditioning sessions. These results show that freezing and avoidance do not quantify context conditioning similarly. They further indicate that lesions to the hippocampus may disrupt the expression of these behaviors used as measures of context conditioning but not the acquisition of context conditioning per se. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Odor-guided fear conditioning in rats: 1. Acquisition, retention, and latent inhibition.

Three experiments examined the acquisition, retention, and latent inhibition of odor-guided fear conditioning in rats. The results of Experiment 1 indicate that forward conditioned stimulus (CS)–unconditioned stimulus (US) pairings resulted in robust freezing responses to subsequent presentation of the CS alone. In Experiment 2, rats in one group (PRE) received unreinforced preexposures to the odorant CS, and those in a second group (NON) were not preexposed to the odorant. All rats then received forward CS–US pairings. PRE rats exhibited a marked attenuation of freezing to subsequent exposure to the CS relative to NON rats. All rats were then retested at one of the following posttraining delays: 17, 24, or 31 days. Freezing behavior of the NON rats declined significantly across these delays, whereas rats in the PRE group froze no more at any delay than they had 24 hr after training. Experiment 3 examined the contextual specificity of latent inhibition. Only those rats that were preexposed and were trained in the same context exhibited latent inhibition. These results indicate that odor-guided fear conditioning is a robust and useful paradigm suitable for future studies of the neural bases of associative learning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Conditional analgesia, defensive freezing, and benzodiazepines.

When rats are placed in a situation that has come to be associated with footshock through the process of Pavlovian conditioning, they react with the species-specific defensive response of freezing and a reduction in sensitivity to painful stimulation. In the present experiments, the effects of three benzodiazepines on both of these responses were examined. Pain sensitivity was measured with the formalin test. Concurrent observations of formalin-induced recuperative behavior and freezing were recorded while the animals were in the presence of shock-associated contextual stimuli. It was found that midazolam (Experiments 1 and 2), chlordiazepoxide (Experiment 3), and diazepam (Experiment 4) were capable of significantly attenuating the conditional analgesia. Midazolam and diazepam also reduced the freezing response. The finding that these anxiolytic agents attenuate both conditional responses suggests that the freezing and analgesia are mediated by a common fearlike process. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Medial Amygdala Modulation of Predator Odor-Induced Unconditioned Fear in the Rat.

This study examined the participation of the medial amygdala (MeA) in unconditioned fear. Rats received ibotenic acid lesions in the MeA or central amygdala (CeA) prior to cat-odor exposure. MeA-lesioned rats exhibited a significant reduction in freezing duration and made frequent contact with a cloth containing cat odor. In contrast, CeA lesions had no significant effects on unconditioned fear. The freezing reduction produced by MeA lesions was not due to a performance deficit because MeA-lesioned rats, unlike CeA-lesioned rats, were capable of freezing in postshock test intervals. Furthermore, MeA lesions did not alter olfactory function and general locomotor activity. Results demonstrate that the MeA plays a major role in modulating predator odor-induced unconditioned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Presynaptic muscarinic cholinergic receptors in the dorsal hippocampus regulate behavioral inhibition of preweanling rats

The aim of this research was to determine whether early maturation of the dorsal hippocampal cholinergic system mediates behavior exhibited by preweanling rats in the presence or absence of an unfamiliar adult male rat, a threatening stimulus. The behavioral responses that were examined included behavioral inhibition or freezing which emerges at 2 weeks of age and ultrasonic vocalizations. Prior to behavioral testing, oxotremorine, an M2 muscarinic receptor agonist that reduces cholinergic release from presynaptic terminals, was infused into the dorsal hippocampal dentate gyrus. Results demonstrated that 14-day-old rats with bilateral hippocampal infusions of a 1 microgram dose of oxotremorine exhibited significant deficits in freezing when exposed to the adult male rat. Importantly, oxotremorine had no significant effects on ultrasound emission and ambulatory activity when rat pups were tested in social isolation. Thus, effects of oxotremorine in the hippocampal dentate gyrus do not produce global changes in behavior. Results suggest that cholinergic release into the dorsal hippocampus facilitates the display of behavioral inhibition at the end of the second postnatal week. Behavioral deficits in freezing may reflect an oxotremorine-induced disruption of hippocampal cholinergic function underlying the processing of biologically relevant olfactory stimuli as well as mechanisms associated with attention.     

Reactivation treatment prevents the memory-impairing effects of scopolamine in preweanling rats.

The authors report that the expression of a conditioned odor aversion is impaired in preweanling rats when they are conditioned on Postnatal Day 12 and tested under the influence of scopolamine hydrobromide (0.2 or 0.5 mg/kg, intraperitoneal) after a 48-hr, but not after a 2-hr, retention interval (Experiment 1). This effect of scopolamine is not dependent on maturation of the cholinergic system between Days 12 and 14 (Experiment 2), nor is it due to peripheral mechanisms (Experiment 3). When pups are reexposed to the unconditioned stimulus (footshock) before drug administration, performance on the 48-hr retention test is not impaired by scopolamine (Experiment 4). These findings demonstrate that the cholinergic system may be critical for the retrieval and expression of long-term or weak memories in young rats. However, the expression of active memories (recent or recently reactivated) may not be dependent on the cholinergic system to the same extent as is the expression of inactive memories. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of the defensive nature of kindling-induced emotionality.

Long-term amygdala kindling produces substantial changes in emotional behavior in rats. The purpose of these experiments was to determine whether kindling-induced emotionality is fundamentally defensive or aggressive in nature. In Experiment 1, amygdala-kindled rats tested as intruders in a resident-intruder paradigm preferred an active defense strategy (i.e., defensive upright stance, jump attacks), whereas the sham-stimulated rats preferred a passive defense strategy (i.e., freezing). In Experiment 2, amygdala-kindled rats explored an unfamiliar open field significantly less than did the sham-stimulated rats, and they were significantly more resistant to capture from the unfamiliar open field than were the sham-stimulated rats. In contrast, them were no significant differences between the kindled and sham-stimulated rats in resistance to capture from their home cages. These results suggest that the emotionality produced by long-term amygdala kindling is fundamentally defensive in nature. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Chronic immobilization stress alters aspects of emotionality and associative learning in the rat.

Chronic stress significantly alters limbic neuroarchitecture and function, and potentiates emotionality in rats. Chronic restraint stress (CRS) increases aggression among familiar rats, potentiates anxiety, and enhances fear conditioning. Chronic immobilization stress (CIS) induces anxiety behavior and dendritic hypertrophy in the basolateral amygdala, which persist beyond a recovery period. However, little else is known about the emotional impact of CIS as a model of chronic stress or depression. Therefore, the authors present two experiments examining emotional and learned responses to CIS. In Experiment I, the authors examine individual differences in behaviors during and after CIS, specifically: struggling, aggression, learned helplessness, inhibitory avoidance, and escape behavior. In Experiment II, the authors confirm the effects of CIS on aggression and struggling during immobilization, and correlate individual responses with aspects of conditioned fear. Here the authors report significant effects of CIS on aggression, inhibitory avoidance, escape, as well as learned aspects of fear (i.e., fear conditioning) and inescapable stress (i.e., struggling and helplessness). These results emphasize the emotional and learned responses to CIS evident during and after the stress treatment, as well as the importance of individual differences. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CS modality transfer of two-way avoidance in rats with central and basolateral amygdala lesions

Post-lesion acquisition of two-way avoidance and subsequent transfer to two warning signals (conditioned stimulus, CS) of different modality were investigated in 60 rats. In Experiment I the animals were originally trained with less salient (darkness) CS, then transferred to more salient compound (darkness and white noise), and finally to white noise CS. The opposite arrangement of the conditioned stimuli (CSi) during the subsequent stages was employed in Experiment II. In control animals, avoidance acquisition was faster and the intertrial responding (ITR) rate lower with the auditory than with the visual CS. Lesioned rats learned avoidance responses more slowly, independently of CS modality. The transfer to other CSi revealed dramatic between-group difference in the level and consistency of avoidance response, shuttle-box latencies and ITR rate. In control animals, transfer to more salient CSi enhanced avoidance performance, whereas change to less salient CS decreased it. Rather small changes in shuttle-box performance and consistency of avoidance response due to CS modality were seen in rats with the basolateral lesions. In contrast, central nucleus injury caused a strong deterioration in the avoidance transfer, especially when the visual CS followed the acoustic one. The results indicate differential involvement of the basolateral and central amygdala nuclei in stimulus-processing mechanisms of instrumental defensive behavior.     

Scopolamine injection into the olfactory bulb impairs short-term olfactory memory in rats.

A previous experiment showed that systemic administration of the muscarinic antagonist scopolamine altered delayed matching in an olfactory task in rats. The present experiment tested whether the impairment could result from blockade of the cholinergic transmission in the first relay structure of the olfactory system, the olfactory bulb. 25 rats served as Ss. The drug was infused directly into both olfactory bulbs before test sessions. Results show that the intrabulbar infusion reproduced the effect of the systemic administration. With a 4-sec delay between target odor and choice test, performances of treated rats remained unchanged; however, with a 30-sec delay, rats performed randomly. Results from a complementary electrophysiological experiment in anesthetized rats support the idea that scopolamine injected into the olfactory bulb was unlikely to have reached more central structures. Further evidence for the involvement of pure sensory areas in short-term memory is concluded. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Partial disruption of fear conditioning in rats with unilateral amygdala damage: correspondence with unilateral temporal lobectomy in humans

Conditioned fear in rats was assessed for the effects of pretraining amygdala lesions (unilateral vs. bilateral) across unconditioned stimulus (US) modalities (white noise vs. shock). In contrast to sham controls, unilateral amygdala lesions significantly reduced conditioned freezing responses, whereas bilateral amygdala lesions resulted in a nearly complete lack of freezing to both the conditioned stimulus (CS) and the context. The lesion effects were more pronounced for CS conditioning but were consistent across US modalities. It was concluded that white noise can serve as an effective US and that unilateral amygdala lesions attenuate but do not eliminate conditioned fear in rats. The results support our interpretation of a recent fear conditioning study in humans (K. S. LaBar, J. E. LeDoux, D. D. Spencer, & E. A. Phelps, 1995).     

Role of pituitary-adrenocortical system in mediating avoidance behavior of rats with septal lesions.

3 experiments with a total of 186 male Sprague-Dawley rats examined the hypothesis that the effects of septal lesions and systemic injections of scopolamine on avoidance acquisition could be attributed to the effects of either of these treatments on ACTH secretion. Septal lesions and scopolamine facilitated 2-way conditioned avoidance response acquisition, and the lesions retarded passive avoidance acquisition. However, neither the injections of dexamethasone, a synthetic glucocorticoid which inhibited ACTH secretion as did septal lesions, nor injections of ACTH which mimicked the facilitatory effects of scopolamine on basal ACTH secretion, affected avoidance in these paradigms. Thus, the main hypothesis was not supported. The finding that scopolamine did not affect passive avoidance indicates that a cholinergic system may not be involved in mediating the suppressive effects of punishment. (26 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

CD44v3 and v6 variant isoform expression correlates with poor prognosis in early-stage vulvar cancer

A single electroconvulsive shock (ECS) or a sham ECS was administered to male 3-4-month-old Wistar rats 1, 2, and 4 h before training in an inhibitory avoidance test and in cued classical fear conditioning (measured by means of freezing time in a new environment). ECS impaired inhibitory avoidance at all times and, at 1 or 2 h before training, reduced freezing time before and after re-presentation of the ECS. These results are interpreted as a transient conditioned stimulus (CS)-induced anxiolytic or analgesic effect lasting about 2 h after a single treatment, in addition to the known amnesic effect of the stimulus. This suggests that the effect of anterograde learning impairment is demonstrated unequivocally only when the analgesic/anxiolytic effect is over (about 4 h after ECS administration) and that this impairment of learning is selective, affecting inhibitory avoidance but not classical fear conditioning to a discrete stimulus.     

Synthetic versus natural cat odorant effects on rodent behavior and medial amygdala plasticity.

Fear and anxiety behaviors are underpinned by neuronal changes within the amygdala. Here, the effects of exposure to natural and synthetic cat odor on behavior and amygdala plasticity were determined. Exposure to natural odor elicited typical and persistent anxiety-related behaviors, such as avoidance, freezing, and flat-back approach; however, synthetic odorant evoked no significant alteration in behavior. Furthermore, ex vivo induction of long-term potentiation within the medial nucleus of the amygdala, a principal area involved in olfactory perception, was significantly reduced after exposure to natural, but not synthetic, odor. Data presented here suggests that the synthetic odorant utilized may lack the constituents that are required to indicate predator presence in rodents and also the capacity to modulate neuronal plasticity within the medial nucleus of the amygdala. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Ontogeny of defensive reactions in Norway rats.

In 3 experiments, 219 Sprague-Dawley albino rats of several ages were presented with stimuli (a caged domestic cat, a footshock, and a suddenly moving object) known to be aversive to adults and disruptive of behavior in mature animals. 20-day-old Ss were relatively unaffected by these events, while Ss aged 30 days and older tended to reduce their locomotion and freeze upon the presentation of these cues. Data are consistent with R. C. Bolles's (1970, 1971) hypothesis that shock-elicited responses are innate defensive reactions. It is suggested that the inefficient passive avoidance learning in juvenile rats may result from their deficit in shock-induced freezing. (41 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)