Predator odor as an unconditioned fear stimulus in rats: Elicitation of freezing by trimethylthiazoline, a component of fox feces.

Four experiments tested whether an odor from a rat predator can unconditionally elicit a fear response in rats. In a large chamber, rats displayed fear-related behaviors to trimethylthiazoline (TMT, a volatile compound isolated from fox feces), including avoidance and immobility, while showing less exploratory behavior. In a smaller chamber, TMT induced a species-typical fear response, freezing, whereas other odors did not. In addition, TMT systematically elicited more freezing as the amount of TMT increased. Moreover, there was no within-sessions or between-sessions habituation of freezing to TMT, nor did TMT promote contextual conditioning. The results indicate that the predator odor, TMT, can induce a fear-related behavioral response in rats that is controllable and quantifiable, suggesting that TMT-induced freezing may be a useful paradigm for a neurobehavioral system analysis of ecologically relevant, unconditioned fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Amygdala kindling-resistant (SLOW) or -prone (FAST) rat strains show differential fear responses

The authors compared two rat strains, selectively bred for their susceptibility to amygdala kindling, with respect to their performance on various behavioral and learning tasks that are associated with fear and anxiety. The two rat strains differed significantly in measurements of exploration of novel and familiar environments, as well as in reactivity to footshock and fear-based learning. The kindling-resistant (SLOW) strain exhibited a lower ratio of open- to closed-arm entries in the elevated plus-maze, less activity over days in the open field, greater behavioral suppression in the open-field if previously footshocked, greater freezing in the inhibitory avoidance task, and slower acquisition and poorer retention in the one-way avoidance task than did the kindling-prone (FAST) strain. These experiments suggest that the SLOW rats are more expressively fearful than the FAST rats, particularly with respect to environmentally triggered freezing or immobility. Further, these observations imply that the relatively constrained excitability of the amygdala network in the SLOW rats might mediate their relatively greater expression of fear and anxiety compared with the FAST rats.     

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)     

Identification of quantitative trait loci involved in contextual and auditory-cued fear conditioning in BXD recombinant inbred strains.

Fear conditioning shows associations formed between contextual or auditory stimuli with an unconditioned stimulus. Inbred mouse strains differ in their ability to demonstrate fear conditioning, suggesting at least a partial genetic influence. The present study identified the possible chromosomal loci regulating fear conditioning in BXD recombinant inbred strains using quantitative trait loci (QTL) analysis. Estimates of heritability for all 3 measures of conditioning were about .28. Correlational analyses between genetic markers and strain means identified multiple putative QTLs. The strongest associations were on Chromosomes 1 and 17 for freezing to the context, Chromosome 12 for freezing to an altered context, and Chromosome 1 for freezing to the auditory stimulus. Overlapping QTLs may indicate some common genes that underlie aspects of this learning task. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Food intake, aggression, and fear behavior in the mother rat: Control by neural systems concerned with milk ejection and maternal behavior.

Mother rats eat more, are more aggressive, and show less fear behavior (freezing) than during other stages of the reproductive cycle. In the present 2 experiments, with 38 female Wistar rats, electrolytic lesions in the peripeduncular area of the lateral midbrain made nursing mothers eat less and interact peacefully with male intruders. Because this midbrain area forms part of the ascending milk-ejection pathway, it is possible that the suckling stimulus may maintain hyperphagia and aggression in mother rats. Since no alteration in fear behavior was observed in mothers with lesions, it was predicted that the reduction in freezing was related primarily to maternal responsiveness to pup cues other than suckling. In line with this hypothesis, it was found that the experimental induction of maternal behavior in ovariectomized, hormone-treated females was associated with a significant decrease in fear behavior, with no concomitant changes in food intake or aggression. (51 ref) (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)     

Differential role of the medial and lateral prefrontal cortices in fear and anxiety.

In the rat, both the medial and lateral prefrontal. cortices (PFC; mPFC and lPFC, respectively) have direct connections with limbic structures that are important in the expression of fear and anxiety. The present study investigated the behavioral effects of excitotoxic lesions of either the mPFC or the lPFC on conditioned and unconditioned fear paradigms. In both unconditioned fear paradigms (open field, elevated plus-maze), lesions of the mPFC decreased anxiety. In fear conditioning, lPFC lesions substantially increased freezing throughout the different phases of the experiment, whereas mPFC lesions increased freezing to contextual cues and showed reduced freezing to discrete cues. These results support the functional role of the PFC in mediating or modulating central states of fear and anxiety and suggest a functional dissociation between the lPFC and mPFC in their role in fear and anxiety. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Comparative behavioral effects between synthetic 2,4,5-trimethylthiazoline (TMT) and the odor of natural fox (Vulpes vulpes) feces in mice.

Synthetic 2,4,5-trimethylthiazoline (TMT)--a component of red fox (Vulpes vulpes) feces--is frequently used to induce unconditioned fear in rodents. Surprisingly, direct comparison between TMT and natural fox feces odor is almost nonexistent. In this study, Experiment 1 compared the avoidance in relation to TMT concentration, natural fox feces, and gender of fox and mice. Results show that the avoidance is (a) higher with either pure or 50% TMT as compared to natural fox feces, whereas the difference is slight with 10% TMT, and (b) significantly higher for the female mouse group compared to the male mouse group with TMT as well as natural fox feces. In addition, no clear difference in effect was observed between male and female fox feces. Experiment 2 compared behavioral parameters recorded as an index of fear and anxiety, general activity, and avoidance in elevated plus-maze and open-field chamber between 10% TMT and natural fox feces in relation to the estrus cycle of the mice. Results show no cycle period effect--except for the avoidance parameter "distance to odorant"--and no different effects between 10% TMT and natural fox feces except for freezing. (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)     

Water deprivation enhances fear conditioning to contextual, but not discrete, conditional stimuli in rats.

Water-deprived and nondeprived rats were fear conditioned with a discrete tone CS and an aversive footshock unconditioned stimulus/stimuli (UCS). 24 and 48 hrs following conditioning, conditional fear to the tone CS and the context cues of the conditioning chamber, respectively, were assessed by measuring freezing behavior. Water deprivation had no effect on baseline responding to either tone or contextual stimuli. Following either 1 or 3 tone-shock pairings, however, water deprivation selectively enhanced conditional freezing to the contextual cues of the training chamber; conditional freezing to the tone was unaffected by water deprivation. These results are consistent with the view that water deprivation affects fear conditioning via an influence on the hippocampus. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Behavioral Changes Induced in Rats by Exposure to Trimethylthiazoline, a Component of Fox Odor.

Trimethylthiazoline (TMT), a component of fox feces, has been used in various studies as a natural predator stimulus to induce autonomic and behavioral signs of fear (e.g., higher levels of stress hormones, freezing, and risk assessment). The present study investigated whether 2 further behavioral signs of fear are induced in rats by TMT exposure: potentiation of the acoustic startle response and inhibition of appetitive behavior. In addition, the authors tested the rats for dose dependency of TMT-induced freezing behavior. The study confirmed that behavioral changes observed during TMT exposure are caused by TMT-induced fear and are dose dependent. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hippocampal lesions impair contextual fear conditioning in two strains of mice.

Two different strains of mice, C57BL/6J and BALB/c, with hippocampal, cortical, or sham lesions, underwent contextual fear conditioning. In both strains, contextual fear, as measured by the freezing response, was significantly impaired in hippocampus-lesioned animals compared with sham control animals. Fear conditioning was not affected in the cortical-lesioned group. Moreover, there was a strain difference in fear conditioning: The C57BL/6J mice exhibited freezing more frequently than the BALB/c mice. Consistent with previous hippocampal lesion studies in rats, these results indicate that contextual fear conditioning in mice also requires the intact hippocampus. This study provides a basis for evaluating hippocampal synaptic mechanisms in relation to contextual fear conditioning in widely available gene knockout or transgenic mice. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Delayed development of fear-potentiated startle in rats.

Examined the developmental emergence of fear-potentiated startle in rats ranging in age from 16 to 75 days. In Exp 1, a pure tone served as the CS and an acoustic startle pulse served as the unconditioned stimulus (UCS) 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 Exp 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. 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. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The role of 5-HT1A receptors in the behavioral responses associated with innate fear.

Fear is a response induced by threatening stimuli and represents an important adaptive system. The serotonin (5-HT) system has been shown to be involved in the modulation of fear responses and anxiety disorders. In preclinical studies, it has been demonstrated that R (+)-8-hydroxy-dipropylaminotetralin (8-OHDPAT), a 5-HT1A agonist, has anxiolytic properties. However, 8-OHDPATs potential role in unconditioned fear has yet to be elucidated. The current study was designed to investigate the effects of 8-OHDPAT on behavioral and HPA axis function in response to an innate fear-inducing stimulus. Pretreatment with 8-OHDPAT resulted in a significant decrease in freezing grooming, and climbing and caused a significant increase in approach after exposure to an extract from fox feces, 2,5-dihyrdo-2,4,5-trimethylthiazoline (TMT), an unconditioned fear-inducing stimulus. Furthermore, 8-OHDPAT pretreatment also resulted in a significant decrease in blood corticosterone levels, a marker of HPA activation. Taken together, these results suggest an additional anxyolitic-like effect of 8-OHDPAT in innate fear paradigms. (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).     

Conditioned behavioral responses to a context paired with the predator odor trimethylthiazoline.

Contextual fear conditioning is the learning of a fear response in a specific context in response to repeated application of aversive stimuli (e.g., foot shocks) or danger-related stimuli (predator odors) within that context. Cat odor, a danger-related stimulus common in laboratory studies of fear in the past, has often been replaced recently with trimethylthiazoline (TMT), a component of fox feces. No contextual fear conditioning in response to TMT has been reported so far, whereas cat odor has often been shown to induce such fear conditioning in rats. Using TMT in both a 1-compartment and a 2-compartment setup, the authors found conditioned fear behavior (expressed as avoidance behavior) in the 2-compartment setup but not--as reported by others--in the 1-compartment setup. Detailed analysis revealed 2 different coping strategies in the 2-compartment setup: Half of the rats showed pronounced avoidance behavior, whereas the other half showed intense risk assessment behavior. These results indicate that expression of conditioned fear behavior in response to a TMT-paired context is dependent on the experimental setup used, as well as the strategy of the individual rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Differences in kindling development in seven outbred and inbred rat strains

The kindling phenomenon, i.e., the progressive development of focal and secondarily generalized seizures upon repeated electrical stimulation of a limbic brain region, occurs in various species, but with marked differences in kindling rate between species and also within the same species. In rats, differences in kindling rates have been reported within the same strain and between different strains, and both genetic and environmental influences are thought to be involved in this variability. In most studies on kindling in rats, outbred strains such as Sprague-Dawley have been used. In the present study, we compared rates of amygdala kindling development in two outbred (Sprague-Dawley, Wistar) and five inbred (Lewis, Fischer 344, ACI, Wistar-Kyoto, Brown Norway) rat strains, including several strains which have not been kindled before. We were particularly interested which parts of the stepwise progression of kindling differ among these strains. Furthermore, the sensitivity of the basolateral amygdala to electrical stimulation was determined before and after kindling. Once daily electrical stimulation of the basolateral amygdala resulted in marked interstrain differences in kindling rates, with Sprague-Dawley and Brown-Norway rats exhibiting the lowest number of stimulations to reach fully kindled (stage 5) seizures, and Lewis rats showing the highest number of the 7 strains. In contrast to the significant differences in number of stimulations to reach the fully kindled state, total (cumulative) afterdischarge duration (ADD) to reach stage 5 did not significantly differ among strains, substantiating that cumulative AD is the principal factor in the acquisition of kindled seizures. Marked differences in ADD of a stage 5 seizure were obtained between strains, with strains kindling rapidly exhibiting longer ADD than strains kindling slowly. Postkindling afterdischarge threshold (ADT) varied significantly among strains, but only 3 of the 7 strains showed a decrease of ADT compared to prekindling values. When the stepwise progression of kindling was evaluated, pronounced interstrain differences were determined in the time spent in the initial phase of kindling, i.e., stage 1 seizures, both in terms of stimulations and cumulative ADD, indicating that variations in kindling rates were predominantly due to the time needed to progress from stage 1 to subsequent stages of the kindling process. The data seem to indicate that inbred rat strains offer an interesting resource for dissecting the underlying genetic basis for phenotypic differences in epileptogenesis as induced by kindling, although the high variability of kindling rates seen within some inbred strains weakens this possibility.     

Effect of context on performance to conditioned stimuli with mixed histories of reinforcement and nonreinforcement.

Five conditioned suppression experiments, with 160 Wistar rats, explored the role of the conditioning history of the conditioned stimulus (CS) in determining the effects of contextual fear on performance to the CS. Contextual fear was produced by postconditioning exposure to unconditioned stimulus/stimuli (UCS) alone in the context of conditioning; it was independently assessed with context-preference tests. When the number of reinforced and nonreinforced trials was equated across extinction, partial reinforcement, and latent inhibition procedures, only the extinction procedure produced a CS whose performance was subsequently affected (i.e., augmented) by contextual fear. Contextual fear's relatively unique augmenting effect on fear of an extinguished CS was abolished by extensive, but not by less extensive, reacquisition training. Results indicate that, depending on the CS's conditioning history, contextual fear either augments or has little effect on fear of the CS. It is suggested that augmentation by context should be viewed as the restoration of fear that is otherwise depressed by extinction. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Naloxone and shock-elicited freezing in the rat.

In the 1st of 6 experiments with 325 Long-Evans rats it was found that the freezing behavior of the rat that occurs following painful electric shock increased when Ss were pretreated with the opiate antagonist naloxone. Freezing was a positive linear function of drug dose and shock intensity (Exp II). Naloxone pretreatment enhanced freezing only when Ss were given 2 or 3 shocks but did not affect freezing when Ss were given only 1 shock or were not shocked at all (Exps III, IV, and V). Naloxone had to be present during shock to increase freezing (Exp VI). Results suggest that when a rat is shocked, it releases endogenous analgesics (endorphins) that make a subsequent shock less aversive. Naloxone, by blocking the endorphin system, makes the shock more aversive than it would normally be. (23 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Constitution and body proportions in different strains of rats. A study of race formation in breeding isolates

(1) There are considerable differences in body constitution in different strains of rats, ranging from very robust to very gracile forms. The differences are greater in the larger males than in the smaller females. (2)Craniofacial and postcranial proportions of the trunk in domesticated strains of rats differ either uniformly or mosaically from the wild form. (3)Nasal shape differs greatly in rats ranging from extreme leptorrhine to extreme platyrrhine forms, giving a total range greater than in human populations. (4)Fisher 344 rats have long tails and extremities and Buffalo and GRL short tails and extremities. (5)Wistar and ACI rats have longer tails than wild rats but do not differ significantly from wild rats in the relative length of their other extremities. (6)The relationship between tail and extremity length is under genetic control which is concordant in Fisher, Buffalo and GRL rats, but discordant in the Lewis, Wistar and ACI strains. (7)There is no connection between relative extremity length and total body constitution since short-limbed strains occupy both the highest (Buffalo) and lowest (GRL) levels o f robusticity, and strains that do not differ in relative extremity length from wild rats differ greatly from each other in constitutional type (Wistar and ACI). (8)Differences of relative extremity length and nasal shape in rats have their parallels in human populations. But in human populations they follow Allen's ecological "rule" and can be duplicated experimentally. In rats here used, however, they do not result from any known ecological pressures, but from the genetic factors acting in breeding isolates.