Christopher O Boyson1, Elizabeth N Holly1,2,3,4, Andrew R Burke1,5, Sandra Montagud-Romero1,6, Joseph F DeBold1, Klaus A Miczek7,8,9,10. 1. Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA. 2. McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA, USA. 3. Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA, USA. 4. Current affiliation: Department of Neuroscience, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 5. Current affiliation: Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, USA. 6. Unidad de Investigación Psicobiología de las Drogodependencias, Departmento de Psicobiología, Universitat de València, València, Spain. 7. Department of Psychology, Tufts University, Bacon Hall, 530 Boston Ave, Medford, MA, 02155, USA. Klaus.Miczek@tufts.edu. 8. Department of Psychiatry, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu. 9. Department of Pharmacology, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu. 10. Department of Neuroscience, Tufts University School of Medicine, Boston, MA, USA. Klaus.Miczek@tufts.edu.
Abstract
RATIONALE: Intermittent social defeat stress engenders persistent neuroadaptations and can result in later increased cocaine taking and seeking. However, there are individual differences in stress-escalated cocaine self-administration behavior, which may be a direct result of individual differences in the manner in which rats experience social defeat stress. OBJECTIVE: The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration. METHODS: Male Long-Evans rats underwent nine intermittent social defeat episodes over 21 days in a three-compartment apparatus permitting approach to and escape from a confrontation with an aggressive resident rat. Rats then self-administered intravenous cocaine, which culminated in a 24-h unlimited access "binge." Behaviors during social defeat and cocaine self-administration were evaluated by principal component analysis (PCA). RESULTS: PCA revealed that the latency to enter the threatening environment was highly predictive of later cocaine self-administration during the 24-h binge. This behavior was not associated with other cocaine-predictive traits, such as reactivity to novelty in an open field, saccharin preference, and motor impulsivity. Additionally, there was no effect of latency to enter a threatening environment on physiological measures of stress, including plasma corticosterone and corticotropin releasing factor (CRF) in the extended amygdala. However, latency to enter the threatening environment was negatively correlated with brain-derived neurotropic factor (BDNF) and its receptor, tyrosine kinase B (TrkB) in the hippocampus. CONCLUSION: These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration.
RATIONALE: Intermittent social defeat stress engenders persistent neuroadaptations and can result in later increased cocaine taking and seeking. However, there are individual differences in stress-escalated cocaine self-administration behavior, which may be a direct result of individual differences in the manner in which rats experience social defeat stress. OBJECTIVE: The present study dissected the discrete behavioral phases of social defeat and analyzed which behavioral characteristics may be predictive of subsequent cocaine self-administration. METHODS: Male Long-Evans rats underwent nine intermittent social defeat episodes over 21 days in a three-compartment apparatus permitting approach to and escape from a confrontation with an aggressive resident rat. Rats then self-administered intravenous cocaine, which culminated in a 24-h unlimited access "binge." Behaviors during social defeat and cocaine self-administration were evaluated by principal component analysis (PCA). RESULTS: PCA revealed that the latency to enter the threatening environment was highly predictive of later cocaine self-administration during the 24-h binge. This behavior was not associated with other cocaine-predictive traits, such as reactivity to novelty in an open field, saccharin preference, and motor impulsivity. Additionally, there was no effect of latency to enter a threatening environment on physiological measures of stress, including plasma corticosterone and corticotropin releasing factor (CRF) in the extended amygdala. However, latency to enter the threatening environment was negatively correlated with brain-derived neurotropic factor (BDNF) and its receptor, tyrosine kinase B (TrkB) in the hippocampus. CONCLUSION: These data suggest that latency to enter a threatening environment is a novel behavioral characteristic predictive of later cocaine self-administration.
Authors: Herbert E Covington; Thomas F Tropea; Anjali M Rajadhyaksha; Barry E Kosofsky; Klaus A Miczek Journal: Psychopharmacology (Berl) Date: 2007-12-19 Impact factor: 4.530