Flunitrazepam in combination with alcohol engenders high levels of aggression in mice and rats

Abstract

Rationale Higher doses of benzodiazepines and alcohol induce sedation and sleep; however, in low to moderate doses these drugs can increase aggressive behavior. Objectives To assess firstly the effects of ethanol, secondly the effects of flunitrazepam, a so-called club drug, and thirdly the effects of flunitrazepam plus alcohol on aggression in mice and rats. Methods Exhaustive behavioral records of confrontations between a male resident and a male intruder were obtained twice a week, using CF-1 mice and Wistar rats. The salient aggressive and non-aggressive elements in the resident´s reperetoire were analyzed. Initially, the effects of ethanol (1.0 g/kg), and secondly flunitrazepam (0; 0.01; 0.1; and 0.3 mg/kg) were determined in all mice and rats; subsequently, flunitrazepam or vehicle, given intraperitoneally (0; 0.01; 0.1; and 0.3 mg/kg) was administered plus ethanol 1.0 g/kg or vehicle via gavage. Results The most significant finding is the escalation of aggression after a moderate dose of ethanol, and a low dose of flunitrazepam. The largest increase in aggressive behaviour occurred after combined flunitrazepam plus ethanol treatment in mice and rats. Conclusions Ethanol can heighten aggressive behavior and flunitrazepam further increases this effect in male mice and rats.

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors

“…Previous studies have reported that alcohol intoxication following acute (single dose) as well as chronic ethanol (multiple experimenter-administered, p.o.) increased aggression-like behavior in (intoxicated) rodents in a resident-intruder confrontation paradigm (de Almeida et al, 2010; Peterson et al, 1989). High aggression in this paradigm was associated with increased anxiety and increased plasma CORT (Patki et al, 2015; Peterson et al, 1989).…”

Lipoic acid and pentoxifylline mitigate nandrolone decanoate-induced neurobehavioral perturbations in rats via re-balance of brain neurotransmitters, up-regulation of Nrf2/HO-1 pathway, and down-regulation of TNFR1 expression

“…Behavioral experiments were performed in the period from the 24 th till the 29 th day of the experiment and during the light cycle from 8 a.m. till 5 p.m. (de Almeida et al, 2010). After the last dose on day 30, all rats were weighed then sacrificed by decapitation.…”

Motivational drive and alprazolam misuse: A recipe for aggression?

“…Controlled laboratory studies have demonstrated that alprazolam and diazepam use can result in an increased aggressive response in some participants (e.g., Bond and Silveira, 1993;Bond et al, 1995;Ben-Porath and Taylor, 2002;Wallace and Taylor, 2009), and animal studies report the possible influence of concurrent alcohol use (de Almeida et al, 2010) and pre-existing aggressive tendencies (Ferrari et al, 1997;Weerts et al, 2010) in benzodiazepine-related aggression.…”