Sensitization is a non-associative learning process in which repeated administration of a stimulation results in the progressive amplification of a response.
History
Eric Kandel was one of the first to study the neural basis of sensitization, conducting experiments in the 1960s and 1970s on the gill withdrawal reflex of the seaslug
Aplysia. Kandel and his colleagues first habituated the reflex, weakening the response by repeatedly touching the animal's siphon. They then paired noxious electrical stimulus to the tail with a touch to the siphon, causing the gill withdrawal response to reappear. After this sensitization, a light touch to the siphon alone produced a strong gill withdrawal response, and this sensitization effect lasted for several days. (After Squire and Kandel, 1999
[Squire LR, Kandel ER (1999). Memory: From Mind to Molecules. New York: Scientific American Library; New York: W.H. Freeman. .]). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes.
Neural substrates
The neural basis of behavioral sensitization is often not known, but it typically seems to result from a cellular receptor becoming more likely to respond to a stimulus. Several examples of neural sensitization include:
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Electrical or chemical stimulation of the rat hippocampus causes strengthening of , a process known as long-term potentiation or LTP.
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In "Kindling model", repeated stimulation of hippocampal or amygdala neurons in the limbic system eventually leads to in laboratory animals. After sensitization, very little stimulation may be required to produce seizures. Thus, kindling has been suggested as a model for temporal lobe epilepsy in humans, where stimulation of a repetitive type (flickering lights for instance) can cause epileptic seizures.
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In "central sensitization", nociceptive neurons in the dorsal horns of the spinal cord become sensitized by peripheral tissue damage or inflammation.
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Drug sensitization occurs in drug addiction, and is defined as an increased effect of drug following repeated doses (the opposite of drug tolerance). Such sensitization involves changes in brain mesolimbic dopamine transmission, as well as a protein inside mesolimbic neurons called delta FosB. An associative process may contribute to addiction, for environmental stimuli associated with drug taking may increase craving. This process may increase the risk for relapse in addicts attempting to quit.
Cross-sensitization
Cross-sensitization is a phenomenon in which sensitization to a stimulus is generalized to a related stimulus, resulting in the amplification of a particular response to both the original stimulus and the related stimulus.
For example, cross-sensitization to the neural and behavioral effects of
are well characterized, such as sensitization to the locomotor response of a stimulant resulting in cross-sensitization to the motor-activating effects of other stimulants. Similarly, reward sensitization to a particular addictive drug often results in reward cross-sensitization, which entails sensitization to the
reward system of other addictive drugs in the same
drug class or even certain
.
In animals, cross-sensitization has been established between the consumption of many different types of Substance abuse – in line with the gateway drug theory – and also between sugar consumption and the self-administration of drugs of abuse.
As a causal factor in pathology
Sensitization has been implied as a causal or maintaining mechanism in a wide range of apparently unrelated pathologies including
addiction, allergies, asthma, overactive bladder
and some medically unexplained syndromes such as
fibromyalgia and multiple chemical sensitivity. Sensitization may also contribute to psychological disorders such as post-traumatic stress disorder,
panic anxiety and
.
See also
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Long-term potentiation
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Multiple chemical sensitivity
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Neuroplasticity
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Synaptic plasticity
