<abstract xmlns="http://www.w3.org/1999/xhtml"> 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 threei. 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.</abstract>

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 threei. 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.

Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats

Department of Physiology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, Belgrade, Serbia

Department of Chemistry and Biochemistry, University of Wisconsin–Milwaukee, Milwaukee, Wisconsin, USA

Acta Veterinaria

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

The complex clinical picture of mono-neuropathy following injury of peripheral nerve is often accompanied by changes in the patients’ affective states. It has...

Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats

Published Online: Jun 17, 2014

Page range: 189 - 199

Received: Dec 31, 2013

Accepted: Mar 13, 2014

DOI: https://doi.org/10.2478/acve-2014-0018

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

© by Lj. Aleksandar Obradović

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Delayed Behavioral Effects of SH–I–048A, a Novel Nonselective Positive Modulator of Gabaa Receptors, After Peripheral Nerve Injury in Rats

Published Online: Jun 17, 2014

Page range: 189 - 199

Received: Dec 31, 2013

Accepted: Mar 13, 2014

DOI: https://doi.org/10.2478/acve-2014-0018

Keywordsbenzodiazepines elevated plus maze, nerve crush injury, spontaneous locomotor activity, Wistar rats

© by Lj. Aleksandar Obradović

This article is distributed under the terms of the Creative Commons Attribution Non-Commercial License, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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