title: Loss of environmental enrichment increases vulnerability to cocaine addiction.
abstract: Life experiences, especially during critical periods of maturation, such as adolescence, can dramatically affect vulnerability to diseases at adulthood. Early exposure to positive environmental conditions such as environmental enrichment (EE) has been shown to reduce the occurrence and the intensity of neurological and psychiatric disorders including drug addiction. However, whether or not exposure to EE during early stages of life would protect from addiction when, at adulthood, individuals may find themselves in non-enriched conditions has not been investigated. Here we show that switching mice from EE to non-enriched standard environments not only results in the loss of the preventive effects of EE but also increases the rewarding effects of cocaine. This enhanced vulnerability is associated with emotional distress and with increased levels in the mRNA levels of corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST), as well as with increases in CREB phosphorylation in the BNST and in the shell of the nucleus accumbens. The increased sensitivity to the rewarding effects of cocaine is completely blocked by the CRF antagonist antalarmin, confirming a major role of the CRF system in the negative consequences of this environmental switch. These results indicate that positive life conditions during early stages of life, if they are not maintained at adulthood, may have negative emotional consequences and increase the risks to develop drug addiction.
authors.affiliation: INSERM U-1084, Experimental and Clinical Neurosciences Laboratory, Neurobiology and Neuropharmacology Addiction Group, Poitiers, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Nader
authors.forename: Claudia
authors.initials: C
authors.lastname: Chauvet
authors.forename: Chauvet
authors.initials: C
authors.lastname: Claudia
authors.forename: Rana El
authors.initials: RE
authors.lastname: Rawas
authors.forename: Laure
authors.initials: L
authors.lastname: Favot
authors.forename: Mohamed
authors.initials: M
authors.lastname: Jaber
authors.forename: Nathalie
authors.initials: N
authors.lastname: Thiriet
authors.forename: Marcello
authors.initials: M
authors.lastname: Solinas
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000235:genetics / Q000378:metabolism; D001522:Behavior, Animal / Q000187:drug effects; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000235:genetics / Q000378:metabolism*; D003346:Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004777:Environment; D006799:Housing, Animal; D008297:Male; D051379:Mice; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012686:Septal Nuclei / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017362:Cyclic AMP Response Element-Binding Protein; D018765:Dopamine Uptake Inhibitors; D003346:Corticotropin-Releasing Hormone; D003042:Cocaine