Brain Health Institute and Department of Psychiatry, Rutgers University, Piscataway, NJ 08854 USA.
Child Health Institute and Department of Neuroscience & Cell Biology, Rutgers University, New Brunswick, NJ 08901, USA.
Sci Adv. 2023 Oct 20;9(42):eadf6039. doi: 10.1126/sciadv.adf6039. Epub 2023 Oct 18.
Cocaine self-administration by male rats results in neuronal and behavioral alterations in offspring, including responses to cocaine. Given the high degree of overlap between the brain systems underlying the pathological responses to cocaine and stress, we examined whether sire cocaine taking would influence fear-associated behavioral effects in drug-naïve adult male and female progeny. Sire cocaine exposure had no effect on contextual fear conditioning or its extinction in either male or female offspring. During cued fear conditioning, freezing behavior was enhanced in female, but not male, cocaine-sired progeny. In contrast, male cocaine-sired progeny exhibited enhanced expression of cue-conditioned fear during extinction. Long-term potentiation (LTP) was robust in the basolateral amygdala (BLA), which encodes fear conditioning, of female offspring but was completely absent in male offspring of cocaine-exposed sires. Collectively, these results indicate that cued fear memory is enhanced in the male progeny of cocaine exposed sires, which also have BLA synaptic plasticity deficits.
雄性大鼠的可卡因自我给药会导致后代的神经元和行为改变，包括对可卡因的反应。鉴于可卡因和应激反应的大脑系统之间存在高度重叠，我们研究了雄性亲鼠的可卡因摄入是否会影响药物-naïve 成年雄性和雌性后代的与恐惧相关的行为效应。亲鼠可卡因暴露对雄性或雌性后代的情境性恐惧条件反射或其消退均无影响。在条件性恐惧条件反射期间，雌性而非雄性可卡因亲代后代的冻结行为增强。相比之下，雄性可卡因亲代后代在消退期间表现出增强的线索条件恐惧表达。在编码恐惧条件反射的外侧杏仁核（BLA）中，雌性后代的长时程增强（LTP）非常强烈，但可卡因暴露亲鼠的雄性后代则完全缺失。总的来说，这些结果表明，可卡因暴露亲鼠的雄性后代的线索性恐惧记忆增强，其外侧杏仁核突触可塑性也存在缺陷。
