Pentobarbital inhibits ketamine-induced dopamine release in the rat nucleus accumbens: a microdialysis study

Dopamine release in the nucleus accumbens (NAC) plays a crucial role in the actions of various psychotropic and addictive drugs. Ketamine and barbiturates have psychotropic effects and addictive properties, but barbiturates prevent ketamine's psychotomimetic effects. We investigated the effects of ketamine and pentobarbital on dopamine release in the NAC. A microdialysis probe was implanted in the NAC in 35 rats, which were randomly assigned to seven groups: a normal saline intraperitoneal injection (ip) group, 50 and 100 mg/kg of ketamine ip groups, 25 and 50 mg/kg of pentobarbital ip groups, and a normal saline or 25 mg/kg of pentobarbital ip followed by 50 mg/kg of ketamine ip groups. Perfusate samples were collected every 20 min, and dopamine concentration was measured by high-performance liquid chromatography. Ketamine at doses of 50 mg/kg and 100 mg/kg significantly increased dopamine release in the NAC. Conversely, pentobarbital significantly decreased dopamine release in the NAC and inhibited the ketamine-induced dopamine release. These data suggest that the dopamine release in the NAC may be involved in ketamine-induced, but not barbiturate-induced, psychotropic effects and addiction. Inhibition of ketamine-induced dopamine release by barbiturates may be a mechanism by which they prevent ketamine emergence reactions.

Ketamine increased dopamine release in the nucleus accumbens, which was inhibited by pentobarbital. The mesolimbic dopamine system may be involved in the psychotomimetic effects of ketamine, and the suppression of ketamine emergence reactions by barbiturates may be because of the inhibition of ketamine-induced dopamine release in the nucleus accumbens.