Interaction between naloxone, chlordiazepoxide and valproic acid evaluated by emotional operant behaviour in the rat.

The effects of chlordiazepoxide (CDP, 5 mg/kg i.p.), the sodium salt of valproic acid (VPA, 200 mg/kg i.p.) and naloxone (Nx, 1 mg/kg s.c.) alone and CDP-Nx, VPA-Nx association on schedule controlled behaviour with signalled unpunished and punished periods, were investigated. Our results show that CDP and VPA under both the unemotional (variable ratio reinforcement schedule 20%) and the emotional (continuous reinforced schedule associated with electric shock) components significantly increase responding in the Skinner box. Nx, on the multiple schedule, non-significantly reduces responding under both components. With CDP-Nx association the increase in responding under the unemotional component is less than in the case of the benzodiazepine alone, while under the emotional component the increase in responding is not appreciably affected. With the VPA-Nx association the responding rate is lower than that of the control under the unemotional component while under the emotional component the increase in responding is reduced compared to the VPA alone. The higher rates of unemotional and emotional responding with both CDP and VPA depend on the dipsogenic and disinhibiting effects by both drugs. The different rate of emotional and unemotional responding with CDP-Nx and VPA-Nx associations indicates a specific influence on GABAergic and other systems by CDP and VPA.