Midazolam Induced Learning and Memory Impairment Is Modulated by Cannabinoid CB1 Receptor Agonist and Antagonist

Background: Memory impairment is a well-known effect of many benzodiazepine compounds which is mediated through their action on gamma-aminobutyric acid type A (GABAA) receptors. On the other hand, cannabinoids can affect learning and memory process through presynaptic modulation of the release of both excitatory glutamate and inhibitory GABA transmitters in brain regions involved in learning and memory. The aim of the present study was to investigate the effect of cannabinoids on memory impairment and long-term potentiation (LTP) reduction properties of the short acting benzodiazepine midazolam.Materials and Methods: One week after insertion of guide cannula by stereotaxic surgery, cannabinoid compounds or midazolam were administered by intracerebroventricular (i.c.v.) injection into lateral ventricle of male rats. Spatial memory task was evaluated using Morris water maze (MWM) test. Electrophysiological evaluation was done by field potential recording of hippocampal neurons in unconscious rats.Results: In MWM test, while i.c.v. administration of AM251 (200 and 500 ng) per se could not change learning and memory function in rats, pretreatment of rats with AM251 (500 ng; i.c.v.) attenuated midazolam-induced memory impairment. In field potential recording, while i.c.v. administration of AM251 (500 ng) and WIN55212-2 (10 μg) did not have any effect on population spike amplitude, pretreatment of rats with both AM251 and WIN55212-2 significantly diminished midazolam-induced PS amplitude reduction in hippocampal neurons.Conclusion: OurOur results suggest the involvement of cannabinoid CB1 receptors in both memory impairment and LTP reduction in hippocampal neurons which was produced by midazolam. This interaction is likely through their effect on both GABAergic and glutamatergic receptors in hippocampus.

Keywords:

Midazolam , AM251 , WIN55212-2 , learning and memory , long-term potentiation , Morris water maze