Tolerance, sensitization and dependence to diazepam in Balb/c mice exposed to a novel open space anxiety test.

Ennaceur, Abdelkader, Michalikova, Simona, van Rensburg, Ruan and Chazot, P L (2010) Tolerance, sensitization and dependence to diazepam in Balb/c mice exposed to a novel open space anxiety test. Behavioural brain research, 209 (1). pp. 154-164. ISSN 1872-7549

[img] PDF (A novel open space anxiety test - Diazepam)
Tolerance,_sensitization_and_dependence_to_diazepam_in_Balbc_mice_exposed_to_a_novel_open_space_anxiety_test1.pdf - Published Version
Restricted to Repository staff only

Download (680kB)


Balb/c mice were exposed to an elevated platform that is extended on two opposite sides with lowered steep slopes. They were tested for 12min per session in 6 successive days. They received i.p. administration of either saline or one dose of diazepam (DZP 0.5, 1, 3mg/kg) in sessions 1-3, and saline in sessions 4 and 5. All groups of mice received a single dose of DZP (1mg/kg) in session 6. DZP produced inverted U-shaped dose-responses on the number of entries into different areas of the apparatus, with a peak in mean response at 1mg/kg whereas its effect on the duration of entries was mostly comparable between the 3 doses. It increased the number of crossings on the surface of the platform and facilitated entries onto the slopes. DZP-treated mice crossed frequently onto and spent longer time on the slopes in sessions 1-3 whereas saline-treated mice remained on the platform in sessions 1-6. Withdrawal of DZP in sessions 4-5 increased the latency of first entry and decreased the number and duration of entries onto the slopes which was reversed with the administration of 1mg/kg of DZP in the next session. This ON-OFF the drug may be due to the half-life of DZP which is very short in mice and rats ( approximately 0.88h). It also indicates that DZP-treated mice did not benefit from previous experience of entries onto the slopes which suggests a possible "state-dependent" effect. Administration of DZP after repeated exposures to the test did not facilitate entries onto the slopes but instead increased significantly the number of crossings on the surface of the platform; this increase was much higher than that observed in mice initially treated with DZP and exposed to the test. There is no evidence of habituation in saline-treated mice: the number of crossings on the platform was comparable between the first 5 sessions of the test. These results demonstrate that repeated exposures to the same anxiogenic environment resulted in avoidance responses developing tolerance and approach responses developing sensitization. They suggest that tolerance and sensitization are two opposite sides of the habituation process to the same stimulus and may account for the maintained state of anxiety.

Item Type: Article
Subjects: Sciences > Pharmacy and Pharmacology
Divisions: Faculty of Applied Sciences > Department of Pharmacy Health and Wellbeing
Health Sciences and Wellbeing Beacon
Units of Assessment > 03 Allied Health Professions, Dentistry, Nursing and Pharmacy (UoA)
Related URLs:
Depositing User: Abdelkader Ennaceur
Date Deposited: 19 Oct 2011 12:06
Last Modified: 20 Sep 2017 02:07

Actions (login required)

View Item View Item


Downloads per month over past year