Sensitization is a non-associative learning process in which repeated administration of a stimulus results in the progressive amplification of a response.[1] Sensitization often is characterized by an enhancement of response to a whole class of stimuli in addition to the one that is repeated. For example, repetition of a painful stimulus may make one more responsive to a loud noise.
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[2]). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes.
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:
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.[12][13] For example, cross-sensitization to the neural and behavioral effects of addictive drugs 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 rewarding property of other addictive drugs in the same drug class or even certain natural rewards.
In animals, cross-sensitization has been established between the consumption of many different types of drugs of abuse – in line with the gateway drug theory – and also between sugar consumption and the self-administration of drugs of abuse.[14]
Sensitization has been implied as a causal or maintaining mechanism in a wide range of apparently unrelated pathologies including addiction, allergies, asthma, overactive bladder[15] 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 mood disorders.[16][17][18]
Despite the importance of numerous psychosocial factors, at its core, drug addiction involves a biological process: the ability of repeated exposure to a drug of abuse to induce changes in a vulnerable brain that drive the compulsive seeking and taking of drugs, and loss of control over drug use, that define a state of addiction. ... A large body of literature has demonstrated that such ΔFosB induction in D1-type [nucleus accumbens] neurons increases an animal's sensitivity to drug as well as natural rewards and promotes drug self-administration, presumably through a process of positive reinforcement ... Another ΔFosB target is cFos: as ΔFosB accumulates with repeated drug exposure it represses c-Fos and contributes to the molecular switch whereby ΔFosB is selectively induced in the chronic drug-treated state.41 ... Moreover, there is increasing evidence that, despite a range of genetic risks for addiction across the population, exposure to sufficiently high doses of a drug for long periods of time can transform someone who has relatively lower genetic loading into an addict.
Substance-use disorder: A diagnostic term in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) referring to recurrent use of alcohol or other drugs that causes clinically and functionally significant impairment, such as health problems, disability, and failure to meet major responsibilities at work, school, or home. Depending on the level of severity, this disorder is classified as mild, moderate, or severe.Addiction: A term used to indicate the most severe, chronic stage of substance-use disorder, in which there is a substantial loss of self-control, as indicated by compulsive drug taking despite the desire to stop taking the drug. In the DSM-5, the term addiction is synonymous with the classification of severe substance-use disorder.