García-Cabrerizo R, Keller B, García-Fuster M J
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.
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.
Neuroscience. 2015 Sep 24;304:302-15. doi: 10.1016/j.neuroscience.2015.07.040. Epub 2015 Jul 26.
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.
鉴于青春期是塑造成人行为的关键时期，且可能使个体在日后生活中易患疾病，本研究的目的是找出青春期中一个易受影响的时期，在此期间可卡因暴露会改变海马体细胞命运调控，并评估青春期可卡因经历对成年期海马体可塑性和行为绝望的长期影响。研究一：雄性大鼠在青春期（出生后早期第33 - 39天、中期第40 - 46天、晚期第47 - 53天）连续7天接受可卡因（15mg/kg，腹腔注射）或生理盐水处理。在青春期过程中（出生后第40天、第47天、第54天），于最后一次给药剂量后24小时评估海马体可塑性（即细胞命运调控、细胞生成）。研究二：在成年期，从行为（即强迫游泳试验，出生后第62 - 63天）和分子（海马体细胞标志物，出生后第64天）水平测量青春期（出生后第33 - 39天或第33 - 46天；7天或14天）可卡因暴露的后果。与其他脑区相比，青春期早期慢性可卡因处理仅使海马体中FADD形式失调，而在青春期中期，海马体中的细胞增殖（Ki - 67）受损且PARP - 1裂解增加（一种细胞死亡标志物）。有趣的是，青春期慢性可卡因暴露并未改变成年大鼠在强迫游泳试验中静止不动的时间。这些结果表明，青春期这种慢性可卡因给药模式并未导致成年期强迫游泳试验所测量的行为绝望（即一种促抑郁症状）的后期表现。
