Rats given continuous access to etonitazene hydrochloride in their drinking water (5 micrograms per milliliter) more than doubled their drug intake while deprived of food. Another group of rats with implanted jugular catheters self-administered etonitazene (10 micrograms per kilogram) intravenously on a continuous reinforcement schedule, and the number of infusions increased significantly on days when they were deprived of food. These results suggest that feeding condition may be a powerful determinant of drug-reinforced behavior.

http://science.sciencemag.org/content/sci/205/4403/319.full.pdf

Food deprivation increases oral and intravenous drug intake in rats

Dysesthesias and self-mutilation in humans and subhumans: a review of clinical and experimental studies.

Previous research has shown that food deprivation markedly increased self-adminstration of a variety of drugs. The present study concerns an extension of the food deprivation effect to a range of doses and other forms of deprivation. In each experiment, etonitazene infusions were continously available to rats under the following sequence of satiation (S) or deprivation (D) sessions: S, S, D, S, S, D, S, S, D, S, S, S. Each infusion contingent upon a lever-press response, and session lenght was 4 hr. In the first experiment, five groups of rats, each receiving a different etonitaze dose: 0 (saline), 5, 10, 20 or 40 μg/kg, were tested under conditions of food satiation (free access) and deprivation (8 g food, sessions). Food deprivation produced no increases in responding maintained by saline, but it produced nearly parallel increases in respon3ing across all drug doses. In the second experiment, effects of water satiation (free access) and deprivation (no water) were tested at the 10 μg/kg etonitaze unit dose. Etonitazene-maintained responding was more than twice as high during water deprivation sessions as during satiation sessions. In the third experiment, rats receiving saline infusion (after brief exposure to 10 μg/kg etonitazene infusions to elevate response rates) did not show any systematic changes in saline-maintained behavior as a result of water deprivation or satiation. In the fourth experiment, rats were allowed continous access to food, water and etonitazene infusions (10 μg/kg). In addition, they were given a drinking solution containing 3% glucose and 0.125% saccharin (G + S). When the rats were deprived of the G + S solution, they showed small but reliable increases in etonitazene self-administration. The present results extend previous findings with food deprivation to a range of doses and other deprivation conditions, suggesting that drug-maintained behavior can be controlled by alterations in a variety of other reinforcing events in the environment.

Increased intravenous drug self-administration during deprivation of other reinforcers

Changes in oral etonitazene self-administration were compared in four groups of rats that were maintained at 100, 95, 85, or 75% of their pre-experimental free-feeding body weights. Etonitazene (5 μg/ml) or water was available for 16 h according to a fixed-ratio (FR) 1 schedule. Each liquid delivery (0.1 ml) was contingent upon a lever-press response. During food deprivation etonitazene intake gradually increased to over two-fold as body weights decreased over 25 sessions; etonitazene intake was inversely proportional to body weight. The 75% weight group showed stereotypy, self-mutilation and large variability in daily etonitazene intake. In another experiment a range of deprivation conditions was studied in a group of six rats with etonitazene (5 μg/ml) or water available on an FR 8 schedule during 1-h sessions. When the rats were gradually food satiated, etonitazene-maintained behavior declined but remained higher than water-maintained behavior; however, when they were abruptly food satiated, etonitazene-maintained behavior decreased to low levels.

Determinants of increased drug self-administration due to food deprivation.

Oral etonitazene self-administration was systematically investigated in two inbred strains of rats, Lewis (LEW) and Fischer 344 (F344). For LEW rats, etonitazene maintained higher rates of lever pressing and was consumed in larger volumes than the water vehicle when the reinforcement schedule was fixed ratio (FR) 8. In contrast, with F344 rats responding did not systematically exceed water values at any etonitazene concentration. LEW rats also drank substantially more etonitazene than F344 rats, and at FR 8 only LEW rats showed the typical inverted U-shaped function between etonitazene concentration and number of responses. For the LEW strain, response rate increased as FR size increased from FR 1 to FR 2 and FR 4, but decreased at FR 8. For the F344 strain, as FR size increased response rate showed small increases, but the response rates were far lower than those of the LEW strain. The results support the conclusion that etonitazene was an effective reinforcer for LEW but not F344 rats. These findings demonstrate genetic differences in opioid reinforcement of operant behavior and indicate that genotype can be an important determinant of whether etonitazene serves as a reinforcer.

Chernov Hi

Papers

Pattern of consumption of etonitazene solutions by naive rats.