Infusions of midazolam into the medial prefrontal cortex produce anxiolytic effects in the elevated plus-maze and shock-probe burying tests.

Previous research has shown that lesions of the medial prefrontal cortex (MPFC) inhibit fear-related behavior in rats (Brain Res. 969 (2003) 183-194). However, at present little is known about the role of specific neurotransmitter receptor systems within the MPFC in the mediation of fear and anxiety. For example, extensive research has demonstrated the effectiveness of benzodiazepines in decreasing fear-related behavior. However, no research has yet been published regarding the effects of micro-infusions of benzodiazepines, or any other GABA-A receptor agonist, into the MPFC. In addition, previous work has suggested that there may be functional differences between the dorsal and ventral subregions of the MPFC in regard to fear and anxiety. Therefore, the present study examined the effects of dorsal and ventral MPFC infusions of the benzodiazepine midazolam in two well-validated animal models of anxiety, the elevated plus maze and the shock probe burying test. The results showed that bilateral (5 microg/side) infusions of midazolam into the MPFC produced anxiolytic effects in both behavioural tests, without affecting general activity or pain sensitivity. Furthermore, these anxiolytic effects were found in both the dorsal and ventral regions of the MPFC. The present findings indicate that the benzodiazepine receptors of the MPFC are capable of modulating fear-related behaviors.