Concurrent etonitazene and water intake in rats: role of taste, olfaction, and auditory stimuli.

Abstract

Etonitazene and water were concurrently available to four rats during daily 1 h sessions in operant conditioning chambers equipped with two levers and two liquid dippers. A food-induced training procedure was used whereby etonitazene drinking was rapidly established by presenting rats with gradually increased drug concentrations with their daily food ration. When food was subsequently removed from the session and given post-session, etonitazene responding persisted. The rats were subsequently trained on fixed-ratio (FR) schedules with concurrent access to etonitazene and water. The number of dipper presentations compared with etonitazene concentrations (0.078–10.0 μg/ml) resulted in a typical inverted U-shaped function while etonitazene intake (μg/kg) increased directly with concentration. After drinking large quantities of etonitazene the rats showed ataxia, hyper-activity, and stereotypy. Extinction tests demonstrated that rats could discriminate between etonitazene and water on the basis of one dipper full of each liquid; the amount of etonitazene in one dipper was 0.0078 μg. Further tests showed that this discrimination was based on taste or immediate post-ingestional feedback rather than olfactory cues. An auditory stimulus was presented concurrently with responses on the drug lever; however, there was no difference in responding for the drug in the presence or absence of this stimulus except at the lowest concentration. After the extinction tests, when the lowest drug concentration was again available with concurrent water, responding was substantially higher in the presence of stimulus associated with availability of etonitazene. The results extend previous work on oral narcotic intake to a lever-press concurrent choice procedure which is sensitive to reinforcing effects of the drug at low concentrations.