Effects of midazolam on acquisition and extinction of conditioned taste aversion memory in rats

Some intravenous anesthetic agents such as midazolam are known to induce anterograde and retrograde amnesia. We analyzed the effect of midazolam by the conditioned taste aversion (CTA) acquisition and retention. After the rats were offered 0.1% sodium saccharin (Sac) as conditioned stimulus (CS), an intraperitoneal (i.p.) injection of several concentrations (5-30mg/kg) of midazolam was followed by an i.p. injection of 0.15M LiCl (2% of body weight) as unconditioned stimulus (US). The rats, which acquired CTA by every CS-US paradigm, strongly avoided Sac on the 1st test day after conditioning and maintained the avoidance for 3 days. We have already reported that Sac intake abruptly increased on the 2nd test day and the almost complete extinction occurred on the 3rd test day after conditioning by injection of subhypnotic dose of propofol before LiCl-injection. In contrast, we found that subhypnotic dose of midazolam suppressed not only CTA acquisition, but also CTA retention. On the other hand, an alpha2-adrenergic blocker, yohimbin (1mg/kg) suppressed only the CTA retention. These results suggest that the subhypnotic doses of midazolam firstly affect the acquisition mechanism of the CTA memory (CTAM), resulting the suppression of the retention of CTAM.