title: Hippocampal cell fate regulation by chronic cocaine during periods of adolescent vulnerability: Consequences of cocaine exposure during adolescence on behavioral despair in adulthood.
abstract: Given that adolescence represents a critical moment for shaping adult behavior and may predispose to disease vulnerability later in life, the aim of this study was to find a vulnerable period during adolescence in which hippocampal cell fate regulation was altered by cocaine exposure, and to evaluate the long-term consequences of a cocaine experience during adolescence in affecting hippocampal plasticity and behavioral despair in adulthood. Study I: Male rats were treated with cocaine (15mg/kg, i.p.) or saline for 7 consecutive days during adolescence (early post-natal day (PND) 33-39, mid PND 40-46, late PND 47-53). Hippocampal plasticity (i.e., cell fate regulation, cell genesis) was evaluated 24h after the last treatment dose during the course of adolescence (PND 40, PND 47, PND 54). Study II: The consequences of cocaine exposure during adolescence (PND 33-39 or PND 33-46; 7 or 14days) were measured in adulthood at the behavioral (i.e., forced swim test, PND 62-63) and molecular (hippocampal cell markers, PND 64) levels. Chronic cocaine during early adolescence dysregulated FADD forms only in the hippocampus (HC), as compared to other brain regions, and during mid adolescence, impaired cell proliferation (Ki-67) and increased PARP-1 cleavage (a cell death maker) in the HC. Interestingly, chronic cocaine exposure during adolescence did not alter the time adult rats spent immobile in the forced swim test. These results suggest that this paradigm of chronic cocaine administration during adolescence did not contribute to the later manifestation of behavioral despair (i.e., one pro-depressive symptom) as measured by the forced swim test in adulthood.
authors.affiliation: Neurobiology of Drug Abuse Group, IUNICS/IdISPa, University of the Balearic Islands, Palma de Mallorca, Spain; Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA), ISCIII, Madrid, Spain.
authors.forename: R
authors.initials: R
authors.lastname: García-Cabrerizo
authors.affiliation: Neurobiology of Drug Abuse Group, IUNICS/IdISPa, University of the Balearic Islands, Palma de Mallorca, Spain; Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA), ISCIII, Madrid, Spain.
authors.forename: B
authors.initials: B
authors.lastname: Keller
authors.affiliation: Neurobiology of Drug Abuse Group, IUNICS/IdISPa, University of the Balearic Islands, Palma de Mallorca, Spain; Redes Temáticas de Investigación Cooperativa en Salud-Red de Trastornos Adictivos (RETICS-RTA), ISCIII, Madrid, Spain. Electronic address: j.garcia@uib.es.
authors.forename: M J
authors.initials: MJ
authors.lastname: García-Fuster
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D003042:Cocaine / Q000008:administration & dosage*; D019970:Cocaine-Related Disorders / Q000503:physiopathology*; D003863:Depression / Q000503:physiopathology; D004195:Disease Models, Animal; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D008297:Male; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D017207:Rats, Sprague-Dawley
chemical_list: D018765:Dopamine Uptake Inhibitors; C505535:Fadd protein, rat; D053200:Fas-Associated Death Domain Protein; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; D003042:Cocaine
keywords: FADD; adolescence; cocaine; hippocampus