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Intravenous saline injection as an interoceptive signal in rats

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Abstract

Rationale

Addictive drugs are commonly delivered in the organism by means of intravenous (i.v.) injections. Since saline mimics the blood environment by basic ionic properties and pH, it is generally assumed that it should not have any physiological effects, serving as a control for the effects induced by drugs.

Objective

The aim of the study was to examine central, behavioral, and physiological effects of stress- and cue-free i.v. saline injection in freely moving rats.

Methods

We examined how a typical low-volume and slow-speed saline injections affect cortical electroencephalograpy (EEG), neck electromyography (EMG), locomotor activity as well as central and peripheral temperatures.

Results

Saline injection made during slow-wave synchronized activity induces rapid transient EEG desynchronization, manifesting as a drop of EEG total power, decrease in alpha activity, and increases in beta and gamma activities. Saline injection did not affect locomotor activity as well as brain and body temperatures, but induced a transient increase in neck EMG activity and a rapid brief drop in skin temperature, suggesting peripheral vasoconstriction. These responses were virtually fully absent when saline injection was made during naturally occurring desynchronized EEG activity during behavioral activity.

Conclusions

Since i.v. injection is able to produce a peripheral sensory signal that is transmitted rapidly to the CNS and followed by a more prolonged effect of the injected drug on brain cells, with repeated drug administrations, the injection itself could play a role of drug-related sensory cue, thus inducing conditioned physiological responses and altering the effects of injected drugs.

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Acknowledgments

This research was supported by the Intramural Research Program of the NIH, NIDA. We wish to thank Jeremy Tang for his participation in exp. 2 of this study.

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Correspondence to Eugene A. Kiyatkin.

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Online Resource 1 Fig. S1

Original examples of changes in EEG and EMG activity following i.v. saline injections made during sleep state. The data are shown for 30 s before and 120 s after i.v. saline injection (arrows at 30 s mark the onset of injection). (JPEG 101 kb)

Online Resource 2 Fig. S2

Mean changes in individual EEG waves in the cortex and VTA following i.v. saline injections in awake state. With one exception (VTA, gamma activity), saline has no significant effects on each EEG frequency in both structures (see text). Vertical hatched lines show the onset of saline injection and filled symbols mark values (VTA gamma) significantly different from the pre-injection baseline. (JPEG 137 kb)

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Kiyatkin, E.A., Lenoir, M. Intravenous saline injection as an interoceptive signal in rats. Psychopharmacology 217, 387–396 (2011). https://doi.org/10.1007/s00213-011-2294-4

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  • DOI: https://doi.org/10.1007/s00213-011-2294-4

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