Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, USA.
Neurobiology of Adolescent Drinking in Adulthood Consortium (NADIA), Center for Development and Behavioral Neuroscience, Department of Psychology, Binghamton University, Binghamton, NY, USA.
Dev Psychobiol. 2021 Jul;63(5):903-914. doi: 10.1002/dev.22099. Epub 2021 Jan 28.
Adolescent intermittent ethanol (AIE) exposure in the rat results in a retention of adolescent-like responsiveness to ethanol into adulthood characterized by enhanced sensitivity to socially facilitating and decreased sensitivity to socially suppressing and aversive effects. Similar pattern of responsiveness to social and aversive effects of the selective glutamate NMDA NR2B receptor antagonist ifenprodil is evident in adolescent rats, suggesting that AIE would also retain this pattern of ifenprodil sensitivity into adulthood. Social (Experiment 1) and aversive (measured via conditioned taste aversion; Experiment 2) effects of ifenprodil were assessed in adult male and female rats following AIE exposure. Sensitivity to the social and aversive effects of ifenprodil was not affected by AIE exposure. Experiment 3 assessed protein expression of vesicular transporters of GABA (vGAT) and glutamate (vGlut2) within the prelimbic cortex and nucleus accumbens in adolescents versus adults and in AIE adults versus controls. vGlut2 expression was higher in adolescents relative to adults within the PrL, but lower in the NAc. AIE adults did not retain these adolescent-typical ratios. These findings suggest that AIE is not associated with the retention of adolescent-typical sensitivity to NR2B receptor antagonism, along with no AIE-induced shift in vGlut2 to vGAT ratios.
在大鼠中，青春期间歇性乙醇（AIE）暴露会导致成年后保持类似于青春期的乙醇反应性，表现为对社交促进作用的敏感性增强，对社交抑制和厌恶作用的敏感性降低。选择性谷氨酸 NMDA NR2B 受体拮抗剂ifenprodil 对社交和厌恶作用的反应模式在青春期大鼠中也很明显，这表明 AIE 也会在成年后保持这种 ifenprodil 敏感性模式。在 AIE 暴露后，评估成年雄性和雌性大鼠中 ifenprodil 的社交（实验 1）和厌恶（通过条件性味觉厌恶测量；实验 2）作用。AIE 暴露并不影响 ifenprodil 对社交和厌恶作用的敏感性。实验 3 评估了青少年与成年大鼠以及 AIE 成年大鼠与对照组之间，在额前皮质和伏隔核内 GABA（vGAT）和谷氨酸（vGlut2）囊泡转运体的蛋白表达。在 PrL 中，青少年的 vGlut2 表达相对成年大鼠更高，但在 NAc 中则更低。AIE 成年大鼠并未保留这些青春期典型的比值。这些发现表明，AIE 与保留 NR2B 受体拮抗作用的青春期典型敏感性无关，也没有 AIE 诱导的 vGlut2 与 vGAT 比值变化。
