Intravenous saline injection as an interoceptive signal in rats

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.

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.

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.

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.

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.