Freezing behavior
Encyclopedia
Freezing behavior is the fearful reaction to specific stimuli
Stimulus (physiology)
In physiology, a stimulus is a detectable change in the internal or external environment. The ability of an organism or organ to respond to external stimuli is called sensitivity....

, most commonly observed by animals. It is caused by the sympathetic nervous system
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...

 to deal with threats. 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
Fight or Flight
Fight or Flight may refer to:* Fight-or-flight response, the biological response of animals to acute stress* "Fight or Flight!" , a song off the album Aneurythm by the American hard rock band Living Syndication...

", but can be shown as rather "fright, fight or flight." In addition, freezing is observed to occur before 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 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 either real cat hair or fake cat hair. Two groups of rats were tested: rats that had been lesioned in the basolateral amygdala and rats that were the control group (or sham-operated group). All rats at first froze briefly then retreated away from the stimulus upon initial contact. The results showed that the rats that were lesioned in the basolateral amygdala froze much less to the cat hair than the control group of rats. As expected, both groups of rats froze for a significantly less time when presented with the fake cat hair stimulus than when in the presence of the real cat hair. It was also shown that the both control group and the lesioned group made less contacts with the real cat hair than the fake cat hair. 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
Avoidance
Avoidance is a 2002 novel by Michael Lowenthal. It was nominated for a Lambda Literary Award in 2003.Avoidance explores the topics of child sexual abuse, hebephilia and pederasty...

. The rats were lesioned with ibotenic acid
Ibotenic acid
Ibotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...

, 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 basolateral amygdala on freezing behavior. It was also found that muscarinic cholinergic activation plays a role in the behavior. That suggests that neurotransmitters, in general, play a role in freezing behavior. Now let us look at other possible neurotransmitters or chemical treatments that may affect this response. Several investigations show that freezing behavior is influenced by the following:
  • Serotonin
  • Antipsychotic Drugs
  • Methamphetamine
  • Inhibitors


Hashimoto et al. investigated the effects of conditioned fear on serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...

 and freezing behavior in rats. Through in vivo
In vivo
In vivo is experimentation using a whole, living organism as opposed to a partial or dead organism, or an in vitro controlled environment. Animal testing and clinical trials are two forms of in vivo research...

 microdialysis
Microdialysis
- The microdialysis technique:Microdialysis is a semi-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 to assess their biochemical functions in...

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

Methamphetamines have also shown that they could 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 5-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
Enzyme inhibitor
An enzyme inhibitor is a molecule that binds to enzymes and decreases their activity. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors. They are also used as herbicides and pesticides...

, as expected, interrupt neurotransmitters and influence freezing behavior. This study examined the effects of monoamine oxidase inhibitors on freezing behavior. Rats were treated with specific inhibitors that target either monoamine oxidase
Monoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...

 A or B. The results showed that acute inhibition of both monoamine oxidase A and B reduce axiety 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. It has also been shown that neurotransmitters and similar chemicals influence freezing behavior as well. In a related manner, hormones, progestogens and estrogen
Estrogen
Estrogens , oestrogens , or œstrogens, are a group of compounds named for their importance in the estrous cycle of humans and other animals. They are the primary female sex hormones. Natural estrogens are steroid hormones, while some synthetic ones are non-steroidal...

, play a role in freezing behavior as well. First, the authors tested the rats in marble burying and conditioned fear when they were in behavioral estrous 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 showed 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 show administration of progesterone or both estrogen and progesterone decreases impulsive burying. Both showed a decrease in freezing behavior. The study concludes that "progesterone and/or estrogen may mediate impulsive and/or avoidant behavior." It is interesting to note the changes in freezing behavior in a female's cycle. Therefore, it is typically more appropriate for tests to be done with males only. Freezing behavior is seen to be great impacted by levels of hormones. However, there may be future studies on whether testosterone influences freezing behavior as well.
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