Brown Russell W, Schlitt Marjorie A, Owens Alex S, DePreter Caitlynn C, Cummins Elizabeth D, Kirby Seth L, Gill W Drew, Burgess Katherine C
Department of Biomedical Sciences, James H. Quillen College of Medicine, East Tennessee State University, Johnson City, Tennessee, USA.
Department of Psychology, East Tennessee State University, Johnson City, Tennessee, USA.
Dev Neurosci. 2018;40(1):64-72. doi: 10.1159/000486391. Epub 2018 Feb 14.
The current study analyzed the effects of environmental enrichment versus isolation housing on the behavioral sensitization to nicotine in the neonatal quinpirole (NQ; dopamine D2-like agonist) model of dopamine D2 receptor supersensitivity, a rodent model of schizophrenia. NQ treatment in rats increases dopamine D2 receptor sensitivity throughout the animal's lifetime, consistent with schizophrenia. Animals were administered NQ (1 mg/kg) or saline (NS) from postnatal day (P)1 to P21, weaned, and immediately placed into enriched housing or isolated in wire cages throughout the experiment. Rats were behaviorally sensitized to nicotine (0.5 mg/kg base) or saline every consecutive day from P38 to P45, and brain tissue was harvested at P46. Results revealed that neither housing condition reduced nicotine sensitization in NQ rats, whereas enrichment reduced sensitization to nicotine in NS-treated animals. The nucleus accumbens (NAcc) was analyzed for glial cell line-derived neurotrophic factor (GDNF), a neurotrophin important in dopamine plasticity. Results were complex, and revealed that NAcc GDNF was increased in animals given nicotine, regardless of housing condition. Further, enrichment increased GDNF in NQ rats regardless of adolescent drug treatment and in NS-treated rats given nicotine, but did not increase GDNF in NS-treated controls compared to the isolated housing condition. This study demonstrates that environmental experience has a prominent impact on the behavioral and the neural plasticity NAcc response to nicotine in adolescence.
本研究分析了环境丰富与隔离饲养对多巴胺D2受体超敏反应的新生喹吡罗（NQ；多巴胺D2样激动剂）模型（一种精神分裂症啮齿动物模型）中尼古丁行为敏化的影响。大鼠接受NQ（1毫克/千克）或生理盐水（NS）处理，从出生后第（P）1天至P21天，断奶后，在整个实验过程中立即放入丰富环境饲养或隔离在铁丝笼中。从P38至P45，大鼠每天连续对尼古丁（0.5毫克/千克碱）或生理盐水产生行为敏化，并在P46采集脑组织。结果显示，两种饲养条件均未降低NQ大鼠对尼古丁的敏化，而丰富环境降低了NS处理动物对尼古丁的敏化。分析伏隔核（NAcc）中胶质细胞源性神经营养因子（GDNF），这是一种在多巴胺可塑性中起重要作用的神经营养因子。结果较为复杂，显示无论饲养条件如何，给予尼古丁的动物中NAcc GDNF均增加。此外，无论青春期药物处理如何，丰富环境均增加了NQ大鼠以及给予尼古丁的NS处理大鼠中的GDNF，但与隔离饲养条件相比，未增加NS处理对照组中的GDNF。本研究表明，环境经历对青春期伏隔核对尼古丁的行为和神经可塑性反应有显著影响。
