Midazolam-induced rapid changes in licking behaviour: evidence for involvement of endogenous opioid peptides

The role of endogenous opioid peptides in the effects of midazolam on ingestive behaviour was investigated using a detailed analysis of licking behaviour in the rat. Midazolam (1.8 mg/kg i.p.) was administered in combination with either flumazenil (10 and 20 mg/kg i.p.) or naloxone (0.1 and 0.3 mg/kg i.p.). The effect on licking patterns during 60-s exposures to a range of concentrations of a fat emulsion (Intralipid) was then recorded. Midazolam significantly increased the total number of licks for Intralipid by increasing the mean bout duration. This effect is consistent with the proposal that benzodiazepines enhance palatability. Flumazenil and naloxone were ineffective when administered alone, but both drugs blocked the effect of midazolam on total number of licks by selectively attenuating mean bout duration. Midazolam also produced a significant decrease in the intrabout lick rate, probably due to the muscle relaxant effects of this drug. This decrease in the intrabout lick rate was reversed by pretreatment with flumazenil but not by naloxone. The results suggest that endogenous opioids may be important for the palatability effects of midazolam, but may not be involved in the muscle relaxant effects of this drug.