Freezing behavior or the freeze response or to be petrified is a reaction to specific

stimuli A stimulus is something that causes a physiological response. It may refer to: * Stimulation ** Stimulus (physiology), something external that influences an activity ** Stimulus (psychology), a concept in behaviorism and perception * Stimulus (eco ...

, most commonly observed in prey animals. When a prey animal has been caught and completely overcome by the predator, it may respond by "freezing up/petrification" or in other words by uncontrollably becoming rigid. Studies typically assess a conditioned freezing behavior response to stimuli that typically or innately do not cause fear, such as a tone or shock. Freezing behavior is most easily characterized by changes in blood pressure and lengths of time in crouching position, but it also is known to cause changes such as shortness of breath, increased heart rate, sweating, or choking sensation. However, since it is difficult to measure these sympathetic responses to fear stimuli, studies are typically confined to simple crouching times. A response to stimuli typically is said to be a " fight or flight", but is more completely described as "fight, flight, or freeze". In addition, freezing is observed to occur before or after a fight or flight response.

Physiology

Studies suggest that specific areas of the brain are known to either elicit or inhibit (in the case of lesions) freezing behavior in subjects. The regions include the

basolateral amygdala The basolateral amygdala, or basolateral complex, consists of the lateral, basal and accessory-basal nuclei of the amygdala. The lateral nuclei receives the majority of sensory information, which arrives directly from the temporal lobe structures, ...

and the hippocampus. One such study, conducted by Ann E. Power et al., investigated the effects of lesions in the basolateral amygdala. Rats were placed in a chamber containing cat hair. Two groups of rats were tested: rats that had been lesioned in the basolateral amygdala and rats that were the control group (which were sham-operated). All rats at first froze briefly then retreated away from the stimulus upon initial contact. The results showed that the lesioned rats froze much less to the cat hair than the rats of the control group. These data infer a connection between the basolateral amygdala and freezing behavior. Another study, conducted by Gisquet-Verrier et al., tested the effects of the hippocampus, in three experiments, on both the freezing behavior and avoidance. The rats were lesioned with

ibotenic acid Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compound and psychoactive drug which occurs naturally in ''Amanita muscaria'' and related species of mushrooms typically found i ...

, and were tested against a control group. They first investigated changes from conditioned fear, and results showed that lesions to the hippocampus did not alter freezing behavior and marginally affected avoidance. Next, they tested single conditioning sessions, and it was found that freezing behavior remained unchanged while avoidance was disrupted. Finally, they tested conditioning with a larger stimulus (footshock intensity). It was found that avoidance was unaltered while freezing behavior decreased. Not only did these investigations show that the hippocampus is involved with freezing behavior, but avoidance and freezing behavior do not seem to have similar ways of being quantified when it comes to fear conditioning.

Neurotransmitters

It has been experimentally tested that particular areas of the brain are involved with freezing behavior. As mentioned before, Ann E. Power investigated the effect of

on freezing behavior. It was also found that

muscarinic Muscarinic acetylcholine receptors, or mAChRs, are acetylcholine receptors that form G protein-coupled receptor complexes in the cell membranes of certain neurons and other cells. They play several roles, including acting as the main end-rece ...

cholinergic activation plays a role in the behavior. That suggests that neurotransmitters, in general, play a role in freezing behavior. Several investigations show that freezing behavior is influenced by the following: *Serotonin *Antipsychotic Drugs *Methamphetamine *Monoamine oxidase inhibitors Hashimoto et al. investigated the effects of conditioned fear on

serotonin Serotonin () or 5-hydroxytryptamine (5-HT) is a monoamine neurotransmitter. Its biological function is complex and multifaceted, modulating mood, cognition, reward, learning, memory, and numerous physiological processes such as vomiting and vas ...

and freezing behavior in rats. Through

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

microdialysis Microdialysis is a minimally-invasive sampling technique that is used for continuous measurement of free, unbound analyte concentrations in the extracellular fluid of virtually any tissue. Analytes may include endogenous molecules (e.g. neurotra ...

, certain concentrations of extracellular serotonin in the rat brain were able to be measured. It was found that conditioned fear stress increased the levels of the serotonin in the medial prefrontal cortex. This increase was correlated with an increased freezing behavior that was observed. The rats were then given an inhibitor for the extracellular serotonin, which resulted in a reduced freezing behavior. It can be suggested from these results that inhibition of serotonin can decrease freezing behavior and, also, anxiety. Not only does serotonin influence freezing behavior, but it has been shown that

antipsychotic drugs Antipsychotics, also known as neuroleptics, are a class of psychotropic medication primarily used to manage psychosis (including delusions, hallucinations, paranoia or disordered thought), principally in schizophrenia but also in a range of oth ...

(APDs), such as clozapine, ORG5222, and olanzapine, affect freezing behavior as well. Drugs were administered

subcutaneously The subcutaneous tissue (), also called the hypodermis, hypoderm (), subcutis, superficial fascia, is the lowermost layer of the integumentary system in vertebrates. The types of cells found in the layer are fibroblasts, adipose cells, and macro ...

to rats 30 minutes before footshock stress. It was observed that, 24 hours following the footshock, freezing behavior was present without shocks. This is interesting to note, since there was a sympathetic response to no stimuli at all. This suggests that antipsychotic drugs alter freezing behavior, making the rats more sensitive to fear stimulus, for example.

Methamphetamine Methamphetamine (contracted from ) is a potent central nervous system (CNS) stimulant that is mainly used as a recreational drug and less commonly as a second-line treatment for attention deficit hyperactivity disorder and obesity. Methamph ...

has also been shown to potentially affect freezing behavior. Tsuchiya et al. conducted a study investigating the effect of methamphetamine pretreatment on freezing behavior. Rats were given the drug over a week, ramping up the doses. After that, there was a five-day period without any drugs administered. The rats were then subjected to conditioned fear stress. Repeated but not single methamphetamine pretreatment resulted in a significantly increased freezing behavior. This evidence suggests that previous exposure to chronic methamphetamine results in an increased sensitivity to subsequent stress than a control group. Just as neurotransmitters influence freezing behavior, inhibitors, as expected, interrupt neurotransmitters and influence freezing behavior. This study examined the effects of

monoamine oxidase inhibitors Monoamine oxidase inhibitors (MAOIs) are a class of drugs that inhibit the activity of one or both monoamine oxidase enzymes: monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B). They are best known as effective antidepressants, espec ...

on freezing behavior. Rats were treated with specific inhibitors that target either

monoamine oxidase Monoamine oxidases (MAO) () are a family of enzymes that catalyze the oxidation of monoamines, employing oxygen to clip off their amine group. They are found bound to the outer membrane of mitochondria in most cell types of the body. The first ...

A or B. The results showed that acute inhibition of both monoamine oxidase A and B reduce anxiety or freezing behavior. However, inhibition of monoamine oxidase A or B alone failed to do so.

Hormones

It has been shown that parts of the brain are involved in freezing behavior and that neurotransmitters and similar chemicals influence freezing behavior, as well. In a related manner, hormones,

progestogens Progestogens, also sometimes written progestagens or gestagens, are a class of natural or synthetic steroid hormones that bind to and activate the progesterone receptors (PR). Progesterone is the major and most important progestogen in the bod ...

and

estrogen Estrogen or oestrogen is a category of sex hormone responsible for the development and regulation of the female reproductive system and secondary sex characteristics. There are three major endogenous estrogens that have estrogenic hormonal acti ...

, also play a role in freezing behavior. First, the authors tested the rats in marble burying and conditioned fear when they were in behavioral

estrous The estrous cycle (, originally ) is the set of recurring physiological changes that are induced by reproductive hormones in most mammalian therian females. Estrous cycles start after sexual maturity in females and are interrupted by anestrous p ...

or diestrous. Female rats in behavioral estrous have elevated levels of these steroid hormones and also elicit more approach and less freezing behavior than diestrous rats. Results demonstrate that rats in this behavioral estrous show less impulsive burying and also less freezing behavior than diestrous rats. The authors then administered progesterone and estrogen in ovariectomized rats and tested them in marble burying and conditioned fear. The results for this experiment demonstrate that administration of progesterone or both estrogen and progesterone decreases impulsive burying. Both demonstrate a decrease in freezing behavior. The study concludes that "progesterone and/or estrogen may mediate impulsive and/or avoidant behavior." Freezing behavior in a female's cycle is seen to be greatly impacted by levels of hormones. However, there may be future studies on whether testosterone influences freezing behavior as well.

References

{{reflist Sympathetic nervous system Stress (biology) Anxiety

Physiology

Neurotransmitters

Hormones

See also

References