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Social Defeat Stress Causes a Switch in the Neural Systems Mediating Benzodiazepine Motivation

Benzodiazepines are widely abused by anxious individuals. Consequently, this thesis modeled anxiety in a mouse model in order to investigate benzodiazepine motivation within this sub-population. Using the Tube test of Social Dominance and the Resident/Intruder Paradigm I investigated whether animals identified as dominant or submissive/defeated would differentially display a preference for 0.25 mg/kg midazolam in a conditioned place preference paradigm. Consistent with my hypotheses, benzodiazepine preference was mediated by negative reinforcement as submissive but not dominant mice displayed a preference for midazolam. Furthermore, different neural systems mediated benzodiazepine preference dependent on the stress status of the animal (acute vs. chronic stress) such that, acutely stressed animals experienced benzodiazepine preference through a dopamine-independent pathway whereas chronically stressed animals experienced benzodiazepine preference through a dopamine-dependent pathway. Within chronically stressed mice, blockade of either D1 or D2 receptors attenuated benzodiazepine preference.

Identiferoai:union.ndltd.org:TORONTO/oai:tspace.library.utoronto.ca:1807/30577
Date07 December 2011
CreatorsDoss, Lilian
Contributorsvan der Kooy, Derek
Source SetsUniversity of Toronto
Languageen_ca
Detected LanguageEnglish
TypeThesis

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