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Intrinsic plasticity: an emerging player in addiction

Nature Reviews Neuroscience volume 16, pages 173–184 (2015)Cite this article

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Abstract

Exposure to drugs of abuse, such as cocaine, leads to plastic changes in the activity of brain circuits, and a prevailing view is that these changes play a part in drug addiction. Notably, there has been intense focus on drug-induced changes in synaptic excitability and much less attention on intrinsic excitability factors (that is, excitability factors that are remote from the synapse). Accumulating evidence now suggests that intrinsic factors such as K+ channels are not only altered by cocaine but may also contribute to the shaping of the addiction phenotype.

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Figure 1: Compartmentalization of synaptic and intrinsic excitability factors within the cell.
Figure 2: Key reward-related neural circuits.
Figure 3: Drug-exposure procedures and animal behavioural models used to approximate human addiction.
Figure 4: Intrinsic-to-synaptic interaction hypotheses.

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Acknowledgements

The authors thank Y. Shaham, B. C. Finger and G. Schoenbaum for reading an early version of this manuscript.

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Authors and Affiliations

  1. Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, 75390–9011, Texas, USA

    Saïd Kourrich

  2. National Institute on Drug Abuse, Intramural Research Program, Baltimore, 21224, Maryland, USA

    Donna J. Calu & Antonello Bonci

  3. Solomon H. Snyder Neuroscience Institute, Johns Hopkins University School of Medicine, Baltimore, 21205, Maryland, USA

    Antonello Bonci

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  1. Saïd Kourrich
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Glossary

Abstinence

A period of no drug use usually occurring after a period of repeated drug use. This term is used to describe both human abstinence, in which subjects voluntarily (rehabilitation) or involuntarily (incarceration) abstain from drug use, and also in animal models of drug relapse, in which abstinence is experimentally imposed (forced) by removing the animals from the drug self-administration environment.

A-type K+ current

A transient K+ current that is activated at subthreshold voltage and therefore plays an important part in the generation of the first action potential. A-type K+ currents were originally subdivided in two subtypes: As (also known as ID), which are mediated by Kv1 channels; and Af (also known as IA), which can be mediated by members from Kv1, Kv3 and Kv4 subfamilies. As currents are slowly inactivating (hundreds of milliseconds) K+ currents, whereas Af are fast-inactivating (tens of milliseconds) K+ currents.

Conditioned place preference

A Pavlovian (classical) conditioning model in which one distinct context is paired with drug injections, whereas another context is paired with vehicle injections during the training phase. In the subsequent testing phase (which is drug-free), the animal's preference for either context is determined by allowing the animal to move between the two contexts. An increase in preference for the drug-associated context serves as a measure of the drug's Pavlovian rewarding effects.

Contingent cocaine injections

Intravenous cocaine injections that are delivered as a consequence of the animal's conditioned responding (commonly a lever press or nose poke) during self- administration procedures. These injections are frequently paired with cues (such as a tone or light) that become associated with drug injections.

Incubation of cocaine craving

A hypothetical process of time-dependent increases in cue-induced cocaine seeking after withdrawal from cocaine self-administration in rats.

Non-contingent cocaine injections

Cocaine injections that are delivered independently of the animal's conditioned response; that is, non-voluntary cocaine injections. In psychomotor sensitization, non-contingent intraperitoneal cocaine injections are commonly administered by the experimenter. Self-administration procedures sometimes use control animals that receive non-contingent intravenous injections that equivalent to linked to the conditioned responding of an actively self-administering animal.

Psychomotor sensitization

A progressive increase in locomotor activity or other activity-related measure (stereotypy) that occurs after repeated injections of cocaine and related drugs.

Reinstatement

The recovery of a learned response (for example, lever-pressing) that occurs when a subject is exposed non-contingently to the unconditioned stimulus (for example, food) after extinction. In studies of reinstatement of drug seeking, reinstatement typically refers to the resumption of drug seeking after extinction following exposure to drugs, drug cues or stressors.

Self-administration

In the context of animal models of drug use and addiction, self-administration refers to a behavioural procedure in which animals perform an operant conditioned response (lever press or nose poke) to receive intravenous drug (that is, cocaine) injections. This procedure allows the animal to control its own drug intake voluntarily and thus more closely models the human condition.

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Kourrich, S., Calu, D. & Bonci, A. Intrinsic plasticity: an emerging player in addiction. Nat Rev Neurosci 16, 173–184 (2015). https://doi.org/10.1038/nrn3877

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