Philpot Rex M, Engberg Melanie E, Wecker Lynn
Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, USA.
Behav Brain Res. 2014 Apr 1;262:101-8. doi: 10.1016/j.bbr.2013.12.014. Epub 2014 Jan 7.
This study determined the effects of adolescent nicotine administration on adult alcohol preference in rats exhibiting high or low behavioral reactivity to a novel environment, and ascertained whether nicotine altered ΔFosB in the ventral striatum (vStr) and prefrontal cortex (PFC) immediately after drug administration or after rats matured to adulthood. Animals were characterized as exhibiting high (HLA) or low (LLA) locomotor activity in the novel open field on postnatal day (PND) 31 and received injections of saline (0.9%) or nicotine (0.56 mg free base/kg) from PND 35 to 42. Ethanol-induced conditioned place preference (CPP) was assessed on PND 68 following 8 days conditioning in a biased paradigm; ΔFosB was measured on PND 43 or PND 68. Following adolescent nicotine exposure, HLA animals demonstrated a CPP when conditioned with ethanol; LLA animals were unaffected. Further, adolescent nicotine exposure for 8 days increased levels of ΔFosB in limbic regions in both HLA and LLA rats, but this increase persisted into adulthood only in LLA animals. Results indicate that adolescent nicotine exposure facilitates the establishment of an ethanol CPP in HLA rats, and that sustained elevations in ΔFosB are not necessary or sufficient for the establishment of an ethanol CPP in adulthood. These studies underscore the importance of assessing behavioral phenotype when determining the behavioral and cellular effects of adolescent nicotine exposure.
本研究确定了青春期给予尼古丁对在新环境中表现出高或低行为反应性的大鼠成年后酒精偏好的影响,并确定尼古丁在给药后或大鼠成年后是否会改变腹侧纹状体(vStr)和前额叶皮层(PFC)中的ΔFosB。在出生后第31天(PND 31),将动物在新奇旷场中表现出的运动活动特征分为高(HLA)或低(LLA),并从PND 35至42接受生理盐水(0.9%)或尼古丁(0.56 mg游离碱/kg)注射。在有偏差的范式中进行8天条件训练后,于PND 68评估乙醇诱导的条件性位置偏爱(CPP);在PND 43或PND 68测量ΔFosB。青春期暴露于尼古丁后,HLA动物在接受乙醇条件训练时表现出CPP;LLA动物未受影响。此外,青春期尼古丁暴露持续8天会增加HLA和LLA大鼠边缘区域的ΔFosB水平,但这种增加仅在LLA动物成年后持续存在。结果表明,青春期尼古丁暴露促进了HLA大鼠乙醇CPP的建立,并且成年后乙醇CPP的建立并不一定需要或足以使ΔFosB持续升高。这些研究强调了在确定青春期尼古丁暴露的行为和细胞效应时评估行为表型的重要性。