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Protein synthesis in dorsal hippocampus supports the drug tolerance induced by prior elevated plus-maze experience.
- Source :
-
Neuroscience [Neuroscience] 2011 Apr 14; Vol. 179, pp. 179-87. Date of Electronic Publication: 2011 Feb 01. - Publication Year :
- 2011
-
Abstract
- Tolerance to the anxiolytic-like effect of drugs may develop because of a memory derived from prior experience in certain apparatuses such as the elevated plus-maze (EPM). Activity in basolateral amygdala was shown to be required for consolidating this knowledge. The dorsal hippocampus (DH) is also implicated in long-term memory consolidation, a process relying on new protein synthesis. It is unknown, however, whether the DH protein synthesis disruption would prevent the phenomenon rendering animals unresponsive to benzodiazepines in the EPM retest. To address this, we bilaterally infused the protein synthesis inhibitor anisomycin (ANI) into the rat DH 0, 3 or 6 h after, or 15 min before, the EPM test. DH infusion of ANI (80 μg) around the time of EPM testing preserved the anxiolysis of the midazolam (MDZ; 0.5 mg/kg, i.p.) in rats retested in the EPM 24 h later, suggesting that information consolidated by DH protein synthesis impacts on the subsequent animal's responsiveness to this drug. To examine whether impaired memory acquisition could also contribute to the prevention of MDZ tolerance seen in EPM-experienced animals infused with ANI before testing, the EPM retest was performed 3 h after testing to coincide with the temporal window in which short-term memory remains, for the reason that this process does not require protein synthesis for its formation. The pretest DH anisomycin infusion's ability to prevent the MDZ tolerance on retesting was now missing. This result confirms a specific action of the ANI on memory consolidation. We also found that rats express further avoidance to open-arms in the EPM retest. However, neither pretest nor posttest DH ANI infusion interfered with this pattern of results exhibited by EPM-experienced rats.<br /> (Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.)
- Subjects :
- Animals
Anisomycin pharmacology
Anti-Anxiety Agents pharmacology
Hippocampus drug effects
Male
Memory drug effects
Memory physiology
Midazolam pharmacology
Protein Biosynthesis drug effects
Protein Synthesis Inhibitors pharmacology
Rats
Rats, Wistar
Drug Tolerance physiology
Hippocampus physiology
Maze Learning physiology
Protein Biosynthesis physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-7544
- Volume :
- 179
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 21284953
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2011.01.057