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The hidden side of drug action: brain temperature changes induced by neuroactive drugs

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Abstract

Rationale

Most neuroactive drugs affect brain metabolism as well as systemic and cerebral blood flow, thus altering brain temperature. Although this aspect of drug action usually remains in the shadows, drug-induced alterations in brain temperature reflect their metabolic neural effects and affect neural activity and neural functions.

Objectives

Here, I review brain temperature changes induced by neuroactive drugs, which are used therapeutically (general anesthetics), as a research tool (dopamine agonists and antagonists), and self-administered to induce desired psychic effects (cocaine, methamphetamine, ecstasy). I consider the mechanisms underlying these temperature fluctuations and their influence on neural, physiological, and behavioral effects of these drugs.

Results

By interacting with neural mechanisms regulating metabolic activity and heat exchange between the brain and the rest of the body, neuroactive drugs either increase or decrease brain temperatures both within (35–39 °C) and exceeding the range of physiological fluctuations. These temperature effects differ drastically depending upon the environmental conditions and activity state during drug administration. This state-dependence is especially important for drugs of abuse that are usually taken by humans during psycho-physiological activation and in environments that prevent proper heat dissipation from the brain. Under these conditions, amphetamine-like stimulants induce pathological brain hyperthermia (>40 °C) associated with leakage of the blood–brain barrier and structural abnormalities of brain cells.

Conclusions

The knowledge on brain temperature fluctuations induced by neuroactive drugs provides new information to understand how they influence metabolic neural activity, why their effects depend upon the behavioral context of administration, and the mechanisms underlying adverse drug effects including neurotoxicity.

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Abbreviations

APO:

Apomorphine

DA:

Dopamine

GFAP:

Glial fibrillary acidic protein

iv:

Intravenous

ip:

Intraperitoneal

METH:

Methamphetamine

MDMA:

3,4-methylenedioxymethamphetamine

NAcc:

Nucleus accumbens

sc:

Subcutaneous

VTA:

Ventral tegmental area

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Acknowledgements

This study was supported by the Intramural Research Program of NIDA-NIH. I wish to thank Drs. Magalie Lenoir and Ken T. Wakabayashi for valuable comments on the matter of this manuscript.

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  1. In-Vivo Electrophysiology Unit, Behavioral Neuroscience Branch, National Institute on Drug Abuse—Intramural Research Program, National Institutes of Health, DHHS, 333 Cassell Drive, Baltimore, MD, 21224, USA

    Eugene A. Kiyatkin

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Kiyatkin, E.A. The hidden side of drug action: brain temperature changes induced by neuroactive drugs. Psychopharmacology 225, 765–780 (2013). https://doi.org/10.1007/s00213-012-2957-9

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