title: Capacity of novelty-induced locomotor activity and the hole-board test to predict sensitivity to the conditioned rewarding effects of cocaine.
abstract: Novelty-seeking in rodents, defined as enhanced specific exploration of novel situations, is considered to predict the response of animals to drugs of abuse and, thus, allow "drug-vulnerable" individuals to be identified. The main objective of this study was to assess the predictive ability of two well-known paradigms of the novelty-seeking trait - novelty-induced locomotor activity (which distinguishes High- and Low-Responder mice, depending on their motor activity) and the hole-board test (which determines High- and Low-Novelty Seeker mice depending on the number of head dips they perform) - to identify subjects that would subsequently be more sensitive to the conditioned rewarding effects of cocaine in a population of young adult (PND 56) and adolescent (PND 35) OF1 mice of both sexes. Conditioned place preference (CPP), a useful tool for evaluating the sensitivity of individuals to the incentive properties of addictive drugs, was induced with a sub-threshold dose of cocaine (1 mg/kg, i.p.). Our results showed that novelty-induced motor activity had a greater predictive capacity to identify "vulnerable-drug" individuals among young-adult mice (PND 56), while the hole-board test was more effective in adolescents (PND 35). High-NR young-adults, which presented higher motor activity in the first ten minutes of the test (novelty-reactivity), were 3.9 times more likely to develop cocaine-induced CPP than Low-NR young-adults. When total activity (1h) was evaluated (novelty-habituation), only High-R (novelty-non-habituating) young-adult male and Low-R (novelty-habituating) female mice produced a high conditioning score. However, only High-Novelty Seeker male and female adolescents and Low-Novelty Seeker female young-adult animals (according to the hole-board test), acquired cocaine-induced CPP. These findings should contribute to the development of screening methods for identifying at-risk human drug users and prevention strategies for those with specific vulnerabilities.
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Arenas
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Daza-Losada
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Infer
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Aguilar
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain.
authors.forename: José
authors.initials: J
authors.lastname: Miñarro
authors.affiliation: Unidad de Investigación Psicobiología de las Drogodependencias, Departamento de Psicobiología, Facultad de Psicología, Universitat de València, Valencia 46010, Spain. Electronic address: marta.rodriguez@uv.es.
authors.forename: Marta
authors.initials: M
authors.lastname: Rodríguez-Arias
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D003216:Conditioning, Operant / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D005106:Exploratory Behavior / Q000187:drug effects; D005260:Female; D016014:Linear Models; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D011930:Reaction Time / Q000187:drug effects; D012201:Reward
chemical_list: D018765:Dopamine Uptake Inhibitors; D003042:Cocaine
keywords: Adolescence; CPP; Cocaine; Mice; Novelty-induced activity; Novelty-seeking