Volume 64 (2014) Issue: 2014 No#2

Delayed behavioral effects of SH–I–048A, a novel nonselective positive modulator of GABAA receptors, after peripheral nerve injury in rats

Author(s): Obradović Lj Aleksandar, Joksimović Srđan, Poe M Michael, Timić Tamara, Cook M James, Savić M Miroslav

Keywords:benzodiazepines elevated plus maze, nerve crush injury, spontaneous locomotor activity, Wistar rats

The complex clinical picture of mono-neuropathy following injury of peripheral nerve is often accompanied by changes in the patients’ affective states. It has been shown that positive allosteric modulators of GABAA receptors can decrease nociceptive transmission in animal pain models. However, recent findings suggest a possibility that at least some of the antinociceptive effects of benzodiazepines, related to neuropathic painful stimuli, may to a significant degree be a consequence of their anxiolytic action. In this study we evaluated the possible delayed effects of SH–I–048A, a newly–synthesized high–efficacy nonselective positive modulator of GABAA receptors, on anxiety–like behavior and locomotor activity in Wistar rats with a previously induced peripheral nerve injury. Assessment of behavioral parameters, using spontaneous locomotor activity and elevated plus maze tests, was performed 48h after completion of single-day three-i.p. injections treatment consisting of zero, one, two or three doses of SH–I–048А(10 mg/kg). In general, rats’ behavior observed 72 h after a moderate peripheral nerve injury did not indicate the persistence of sequelae of mono-neuropathic pain. The rats treated with three doses of SH–I–048А displayed an enhanced immobility time in the locomotor activity test, without concomitant decrease of the total distance traveled. On the other hand, in the group treated with two doses of SH–I–048А, a decrease in the emotional reactivity in the elevated plus maze test was observed. Subtle changes in the regimen of dosing of SH–I–048А affect locomotor activity and anxiety-related behavior in animals with peripheral nerve injury.