[Behavioral correlations of gradual forced administration of psychoactive drugs]

The study was aimed at evaluating the behavioral correlations of the forced administration of psychoactive drugs. Wistar rats received the following drugs in elevated doses (over 4 days, i. p.): (i) physiological saline (control; 0.1-0.2-0.4-0.8 ml/rat), (ii) psychostimulant amphetamine (0.5-1.0--2.0-4.0 mg/kg); (iii) opioid analgetic fentanyl (0.00625-0.0125--0.025-0.05 mg/kg), (iv) ethanol 40% solution (0.5-1.0--2.0-4.0 g/kg), (v) barbiturate sodium ethaminal (2.5-5--10-20 mg/kg); and(vi) synthetic glucocorticoid dexamethasone (0.5-1.0--2.0-4.0 mg/kg). The forced regime of drug administration led to gradual load of the organism and prevented drug tolerance. The dynamics of self-stimulation reaction of the lateral hypothalamus was registered every day over drug administration period and revealed the following regularities: (I) dose-dependent effect of psychostimulant amphetamine and opioid analgetic fentanyl; (II) dexamethasone modulated self-stimulation, increasing (2 day, 1 mg/kg) or decreasing it (3 day, 2 mg/kg); (III) ethanol (1-2 g/kg) activated self-stimulation slightly; (IV) sodium ethaminal slightly inhibited self-stimulation and increased the thresholds of self-stimulation. In 24 h and 72 h after the last administration of drugs, the rat behavior was assessed in open field, elevated plus maze, resident-intruder paradigm, and Porsolt's test. In the open field, significant signs of post-intoxication exposure of psychoactive drugs were revealed, which were registered for 24-72 h after drug withdrawal. The withdrawal of drugs was accompanied with reduction (in 24 h) and subsequent recovery (in 72 h) of the vertical motor activity, exploration behavior, and emotionality. The anxiety indexes were increased up to the 3rd day after withdrawal. The antidepressant effect was also increased. The system of aggression-defense was restored only in rats treated with ethanol. The indexes of individual behavior and communicability in the post-intoxication period were decreased as well. It is suggested that the forced regime of drug administration in increasing doses with subsequent withdrawal of drug injections is a suitable method to evaluate the behavioral elements of drug dependence.