title: Lifelong, central corticotropin-releasing factor (CRF) overexpression is associated with individual differences in cocaine-induced conditioned place preference.
abstract: Stress, through corticotropin-releasing factor (CRF), influences all aspects of cocaine addiction. Earlier studies suggest that individual differences in responsivity to stress affect susceptibility to develop addiction. We have previously found that CRF over-expression alters individual differences in behavioural responses to novelty stress in mice. Therefore, we hypothesised that post-natal, long-term over-expression of brain CRF may alter the rewarding effects of cocaine in a manner that is sensitive to individual differences. In this study we specifically investigated cocaine-induced conditioned place preference (CPP) in transgenic mice over-expressing CRF (CRF-OE) and in wild-type (WT) littermates after determining their individual locomotor and emotional responsivity to inescapable novelty. CRF-OE mice showed decreased overall locomotor activity and increased anxiety-like behaviour in response to novelty compared to WT mice. Low behavioural reactivity to novelty (LR) was associated with heightened anxiety-like behaviour in CRF-OE, but not in WT, mice. WT and CRF-OE mice developed CPP equally to both low (5mg/kg) and high (20mg/kg) doses of cocaine. However, LR CRF-OE mice expressed significantly stronger cocaine CPP than transgenic mice with high locomotor response to novelty (HR). In WT mice, on the other hand, stronger CPP induced by 20mg/kg of cocaine was found in the HR animals. Furthermore, there was a strong negative correlation between locomotor reactivity to novelty and CPP in CRF-OE, but not in WT, mice. Collectively, these results suggest that long-term, post-natal CRF over-expression increases the rewarding effects of cocaine in individuals with high emotional response to stress.
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB1 2PD, United Kingdom.
authors.forename: Maki
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Department of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, The Netherlands; Rudolf Magnus Institute of Neuroscience, Utrecht University, The Netherlands.
authors.forename: Lucianne
authors.initials: L
authors.lastname: Groenink
authors.affiliation: Department of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, The Netherlands; Rudolf Magnus Institute of Neuroscience, Utrecht University, The Netherlands.
authors.forename: Elisabeth Y
authors.initials: EY
authors.lastname: Bijlsma
authors.affiliation: Department of Pharmacology, Utrecht Institute of Pharmaceutical Sciences, Utrecht University, The Netherlands; Rudolf Magnus Institute of Neuroscience, Utrecht University, The Netherlands; Department of Psychiatry, Yale University, New Haven, CT, USA.
authors.forename: Berend
authors.initials: B
authors.lastname: Olivier
authors.affiliation: Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB1 2PD, United Kingdom; Discipline of Physiology and Pharmacology, Faculty of Medicine, Health and Molecular Sciences, James Cook University, Townsville, QLD 4811, Australia; Australian Institute of Tropical Health and Medicine, James Cook University, Townsville, QLD, Australia; Comparative Genome Centre, James Cook University, Townsville, QLD, Australia; Centre for Biodiscovery and Molecular Development of Therapeutics, James Cook University, Townsville, QLD, Australia. Electronic address: zoltan.sarnyai@jcu.edu.au.
authors.forename: Zoltán
authors.initials: Z
authors.lastname: Sarnyai
mesh_terms: D000818:Animals; D003042:Cocaine / Q000494:pharmacology*; D003213:Conditioning, Psychological / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005106:Exploratory Behavior / Q000187:drug effects; D007206:Individuality; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009043:Motor Activity / Q000187:drug effects
chemical_list: D003346:Corticotropin-Releasing Hormone; D003042:Cocaine
keywords: Cocaine; Corticotropin-releasing factor; Individual differences; Place preference; Stress; Transgenic mice