Sensitization

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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.

Contents

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 [2] ). In 2000, Eric Kandel was awarded the Nobel Prize in Physiology or Medicine for his research in neuronal learning processes.

Neural substrates

Addiction and dependence glossary [3] [4] [5]
  • addiction – a biopsychosocial disorder characterized by persistent use of drugs (including alcohol) despite substantial harm and adverse consequences
  • addictive drug – psychoactive substances that with repeated use are associated with significantly higher rates of substance use disorders, due in large part to the drug's effect on brain reward systems
  • dependence – an adaptive state associated with a withdrawal syndrome upon cessation of repeated exposure to a stimulus (e.g., drug intake)
  • drug sensitization or reverse tolerance – the escalating effect of a drug resulting from repeated administration at a given dose
  • drug withdrawal – symptoms that occur upon cessation of repeated drug use
  • physical dependence – dependence that involves persistent physical–somatic withdrawal symptoms (e.g., fatigue and delirium tremens)
  • psychological dependence – dependence socially seen as being extremely mild compared to physical dependence (e.g., with enough willpower it could be overcome)
  • reinforcing stimuli – stimuli that increase the probability of repeating behaviors paired with them
  • rewarding stimuli – stimuli that the brain interprets as intrinsically positive and desirable or as something to approach
  • sensitization – an amplified response to a stimulus resulting from repeated exposure to it
  • substance use disorder – a condition in which the use of substances leads to clinically and functionally significant impairment or distress
  • tolerance – the diminishing effect of a drug resulting from repeated administration at a given dose

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

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]

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 [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]

See also

Related Research Articles

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<span class="mw-page-title-main">Dextroamphetamine</span> CNS stimulant and isomer of amphetamine

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<span class="mw-page-title-main">Nucleus accumbens</span> Region of the basal forebrain

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<span class="mw-page-title-main">Methamphetamine</span> Central nervous system stimulant

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<span class="mw-page-title-main">FOSB</span> Protein

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Behavioral addiction, process addiction, or non-substance-related disorder is a form of addiction that involves a compulsion to engage in a rewarding non-substance-related behavior – sometimes called a natural reward – despite any negative consequences to the person's physical, mental, social or financial well-being. In the brain's reward system, a gene transcription factor known as ΔFosB has been identified as a necessary common factor involved in both behavioral and drug addictions, which are associated with the same set of neural adaptations.

<span class="mw-page-title-main">Addiction</span> Disorder resulting in compulsive behaviours

Addiction is a neuropsychological disorder characterized by a persistent and intense urge to use a drug or engage in a behaviour that produces natural reward, despite substantial harm and other negative consequences. Repetitive drug use often alters brain function in ways that perpetuate craving, and weakens self-control. This phenomenon – drugs reshaping brain function – has led to an understanding of addiction as a brain disorder with a complex variety of psychosocial as well as neurobiological factors that are implicated in addiction's development. Classic signs of addiction include compulsive engagement in rewarding stimuli, preoccupation with substances or behavior, and continued use despite negative consequences. Habits and patterns associated with addiction are typically characterized by immediate gratification, coupled with delayed deleterious effects.

Cocaine addiction is the compulsive use of cocaine despite adverse consequences. It arises through epigenetic modification and transcriptional regulation of genes in the nucleus accumbens.

Addiction is a state characterized by compulsive engagement in rewarding stimuli, despite adverse consequences. The process of developing an addiction occurs through instrumental learning, which is otherwise known as operant conditioning.

Addiction vulnerability is an individual's risk of developing an addiction during their lifetime. There are a range of genetic and environmental risk factors for developing an addiction that vary across the population. Genetic and environmental risk factors each account for roughly half of an individual's risk for developing an addiction; the contribution from epigenetic risk factors to the total risk is unknown. Even in individuals with a relatively low genetic risk, exposure to sufficiently high doses of an addictive drug for a long period of time can result in an addiction. In other words, anyone can become an individual with a substance use disorder under particular circumstances. Research is working toward establishing a comprehensive picture of the neurobiology of addiction vulnerability, including all factors at work in propensity for addiction.

References

  1. ↑ Shettleworth, S. J. (2010). Cognition, Evolution and Behavior (2nd ed.). New York: Oxford.
  2. ↑ Squire LR, Kandel ER (1999). Memory: From Mind to Molecules. New York: Scientific American Library; New York: W.H. Freeman. ISBN   0-7167-6037-1.
  3. ↑ Nestler EJ (December 2013). "Cellular basis of memory for addiction". Dialogues in Clinical Neuroscience. 15 (4): 431–443. PMC   3898681 . PMID   24459410. 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.
  4. ↑ Malenka RC, Nestler EJ, Hyman SE (2009). "Chapter 15: Reinforcement and Addictive Disorders". In Sydor A, Brown RY (eds.). Molecular Neuropharmacology: A Foundation for Clinical Neuroscience (2nd ed.). New York: McGraw-Hill Medical. pp. 364–375. ISBN   9780071481274.
  5. ↑ Volkow ND, Koob GF, McLellan AT (January 2016). "Neurobiologic Advances from the Brain Disease Model of Addiction". New England Journal of Medicine. 374 (4): 363–371. doi:10.1056/NEJMra1511480. PMC   6135257 . PMID   26816013. 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.
  6. ↑ Collingridge, Graham L.; Isaac, John T. R.; Wang, Yu Tian (2004). "Receptor trafficking and synaptic plasticity". Nature Reviews Neuroscience. 5 (12): 952–962. doi:10.1038/nrn1556. PMID   15550950. S2CID   15918122.
  7. ↑ Morimoto, Kiyoshi; Fahnestock, Margaret; Racine, Ronald J. (2004). "Kindling and status epilepticus models of epilepsy: Rewiring the brain". Progress in Neurobiology. 73 (1): 1–60. doi:10.1016/j.pneurobio.2004.03.009. PMID   15193778. S2CID   36849482.
  8. ↑ Teicher, M. H.; Glod, C. A.; Surrey, J.; Swett Jr, C. (1993). "Early childhood abuse and limbic system ratings in adult psychiatric outpatients". The Journal of Neuropsychiatry and Clinical Neurosciences. 5 (3): 301–6. doi:10.1176/jnp.5.3.301. PMID   8369640.
  9. ↑ Ji, R. R.; Kohno, T.; Moore, K. A.; Woolf, C. J. (2003). "Central sensitization and LTP: Do pain and memory share similar mechanisms?". Trends in Neurosciences. 26 (12): 696–705. doi:10.1016/j.tins.2003.09.017. PMID   14624855. S2CID   14214986.
  10. ↑ Gudin, J. (2004). "Expanding Our Understanding of Central Sensitization". Medscape Neurobiology. 6 (1).
  11. ↑ Robinson, T. E.; Berridge, K. C. (1993). "The neural basis of drug craving: An incentive-sensitization theory of addiction". Brain Research. Brain Research Reviews. 18 (3): 247–91. doi:10.1016/0165-0173(93)90013-p. hdl: 2027.42/30601 . PMID   8401595. S2CID   13471436.
  12. ↑ Brumovsky PR, Gebhart GF (February 2010). "Visceral organ cross-sensitization – an integrated perspective". Autonomic Neuroscience: Basic & Clinical. 153 (1–2): 106–15. doi:10.1016/j.autneu.2009.07.006. PMC   2818077 . PMID   19679518.
  13. ↑ Malykhina AP, Wyndaele JJ, Andersson KE, De Wachter S, Dmochowski RR (March 2012). "Do the urinary bladder and large bowel interact, in sickness or in health? ICI-RS 2011". Neurourology and Urodynamics. 31 (3): 352–8. doi:10.1002/nau.21228. PMC   3309116 . PMID   22378593.
  14. ↑ Avena NM, Rada P, Hoebel BG (2008). "Evidence for sugar addiction: behavioral and neurochemical effects of intermittent, excessive sugar intake". Neuroscience and Biobehavioral Reviews. 32 (1): 20–39. doi:10.1016/j.neubiorev.2007.04.019. PMC   2235907 . PMID   17617461.
  15. ↑ Reynolds WS, Dmochowski R, Wein A, Bruehl S (August 2016). "Does central sensitization help explain idiopathic overactive bladder?". Nature Reviews. Urology. 13 (8): 481–91. doi:10.1038/nrurol.2016.95. PMC   4969200 . PMID   27245505.
  16. ↑ Rosen, Jeffrey B.; Schulkin, Jay (1998). "From normal fear to pathological anxiety". Psychological Review. 105 (2): 325–350. doi:10.1037/0033-295X.105.2.325. PMID   9577241.
  17. ↑ Antelman, Seymour M. (1988). "Time-dependent sensitization as the cornerstone for a new approach to pharmacotherapy: Drugs as foreign/Stressful stimuli". Drug Development Research. 14: 1–30. doi:10.1002/ddr.430140102. S2CID   144698255.
  18. ↑ Post, R. M. (1992). "Transduction of psychosocial stress into the neurobiology of recurrent affective disorder". The American Journal of Psychiatry. 149 (8): 999–1010. doi:10.1176/ajp.149.8.999. PMID   1353322.
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