A model of fear and pain is presented in which the two are assumed to activate totally different classes of behavior. Fear, produced by stimuli that are associated with painful events, results in defensive behavior and the inhibition of pain and pain-related behaviors. On the other hand, pain, produced by injurious stimulation, motivates recuperative behaviors that promote healing. In this model injurious stimulation, on the one hand, and the expectation of injurious stimulation, on the other hand, activate entirely different motivational systems which serve entirely different functions. The fear motivation system activates defensive behavior, such as freezing and flight from a frightening situation, and its function is to defend the animal against natural dangers, such as predation. A further effect of fear motivation is to organize the perception of environmental events so as to facilitate the perception of danger and safety. The pain motivation system activates recuperative behaviors, including resting and body-care responses, and its function is to promote the animal's recovery from injury. Pain motivation also selectively facilitates the perception of nociceptive stimulation. Since the two kinds of motivation serve different and competitive functions, it might be expected that they would interact through some kind of mutual inhibition. Recent research is described which indicates that this is the case. The most important connection is the inhibition of pain by fear; fear has the top priority. This inhibition appears to be mediated by an endogenous analgesic mechanism involving the endorphins. The model assumes that fear triggers the endorphin mechanism, thereby inhibiting pain motivation and recuperative behaviors that might compete with effective defensive behavior.

A perceptual-defensive-recuperative model of fear and pain

The elevated “zero-maze” is a modification of the elevated plus-maze model of anxiety in rats which incorporates both traditional and novel ethological measures in the analysis of drug effects. The novel design comprises an elevated annular platform with two opposite enclosed quadrants and two open, removing any ambiguity in interpretation of time spent on the central square of the traditional design and allowing uninterrupted exploration. Using this model, the reference benzodiazepine anxiolytics, diazepam (0.125–0.5 mg/kg) and chlordiazepoxide (0.5–2.0 mg/kg) significantly increased the percentage of time spent in the open quadrants (% TO) and the frequency of head dips over the edge of the platform (HDIPS), and reduced the frequency of stretched attend postures (SAP) from the closed to open quadrants. In contrast, the anxiogenic drugm-chlorophenyl-piperazine (mCPP; 0.25–1.0 mg/kg) induced the opposite effects, decreasing %TO and HDIPS, and increasing SAP. The 5-HT1A receptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT; 0.001–0.1 mg/kg) had no effects on either %TO or HDIPS, but did decrease SAP at 0.01 mg/kg although not at higher or lower doses. Similarly, the 5-HT3 receptor antagonist, ondansetron (0.0001–1.0 mg/kg) decreased SAP and increased %TO at 0.01 mg/kg, but not at other doses. The present data suggest that a combination of the novel “zero-maze” design and a detailed ethological analysis provides a sensitive model for the detection of anxiolytic/anxiogenic drug action.

Behavioural and pharmacological characterisation of the elevated "zero-maze" as an animal model of anxiety.

It has been suggested that "phylogenetically prepared fear reactions" may be useful behavioral assays of the effects of anxiolytic agents. In the present experiments, rats' natural proclivity to stay near the perimeters of a novel environment (i.e., thigmotaxis) was suppressed by anxiolytic agents (diazepam 1-5 mg/kg; chlordiazepoxide 1-10 mg/kg; pentobarbital 1-10 mg/kg), with a relative potency that was similar to their relative potency in the treatment of human anxiety. Furthermore, when effects on general activity were factored out using analysis of covariance, the test also showed some degree of drug-class specificity, since neither d-amphetamine, morphine, nor chlorpromazine produced this anti-thigmotaxic effect. These results support an earlier report that thigmotaxis may be a useful test for anxiolytic activity in rats.

Thigmotaxis as a test for anxiolytic activity in rats.

Untreated rats normally avoid the open arms of the "elevated plus-maze," preferring instead the closed arms, whereas rats treated with antianxiety drugs (e.g., diazepam) show far less open-arm avoidance. Although it has often been assumed that rats avoid the open arms because of novelty, height, or open space, the anxiogenic role of these stimuli in the plus-maze has not been systematically examined. In Experiment 1, rats were repeatedly exposed to the elevated plus-maze with the expectation that their "fear" of the open arms would habituate over trials. Instead, open-arm avoidance actually increased on the second trial and showed no evidence of habituating after 18 trials. In Experiment 2, three 30-min sessions of confinement to the open arms ("flooding") failed to decrease rats' open-arm avoidance. Instead, rats that had received flooding avoided the open arms significantly more than control rats during the first test. Experiment 3 showed that although diazepam-treated rats avoided the open arms less than vehicle-controls on the first test this difference dissipated across test trials. Further, diazepam had no carryover effect on rats' subsequent avoidance of the open arms in a nondrugged state. In Experiment 4, plus-maze height was varied from 50 to 6 cm, but rats did not display more open-arm activity as maze height decreased. In Experiment 5, height cues were manipulated by placing a "floor" 8 cm beneath one open arm while leaving the floor of the other open arm at 50 cm. Rats did not avoid the "low" open arm less than the "high" open arm.(ABSTRACT TRUNCATED AT 250 WORDS)

Anxiogenic stimuli in the elevated plus-maze

This paper describes a current psychobiological approach to motivated behavior using fear as an illustration. The first part describes the properties of fear motivation and then argues that an amygdala-periaqueductal gray system displays many of these properties. The second half of the paper details the organization of fear related behavior and then presents a model suggesting how the periaqueductal gray may be responsible for much of this organization.

Michael J. Kelley

Papers

Species-specific behavior and acquisition of avoidance behavior in rats.