Pajser Alisa, Fisher Hayley, Pickens Charles L
Department of Psychological Sciences, Kansas State University, Manhattan, KS 66506, USA.
Department of Psychological Sciences, Kansas State University, Manhattan, KS 66506, USA.
Physiol Behav. 2021 Feb 1;229:113212. doi: 10.1016/j.physbeh.2020.113212. Epub 2020 Oct 16.
Our previous research has shown a relationship between low voluntary alcohol consumption and high conditioned fear in male Long Evans rats. Here, we examined whether differences in the endogenous opioid systems might be responsible for these differences. Rats received 6 weeks of chronic intermittent to 20% alcohol (v/v) or water-only from PND 26-66. Based on their consumption during the last 2 weeks of alcohol access, the alcohol-access rats were divided into high drinking (>2.5 g/kg/24-h) or low drinking (<2 g/kg/24-h). Rats were then given injections of the preferential mu opioid receptor antagonist naltrexone (1 mg/kg, s.c.) or the selective kappa opioid receptor antagonist LY2456302 (10 mg/kg, s.c.) prior to fear conditioning and were then tested for conditioned fear 2 days later. Pre-training naltrexone increased conditioned suppression of lever-pressing during training and testing, with no differences between high versus low alcohol drinkers or between water-only versus alcohol access groups (averaged across drinking levels). There was no effect of LY2456302 on conditioned fear in any comparison. We also found no differences between high and low alcohol drinkers and no reliable effect of prior alcohol access (averaged across drinking levels) on conditioned fear. Our experiment replicates and extends previous demonstrations that a preferential MOR antagonist can increase fear learning using conditioned suppression of lever-pressing as a fear measure. However, additional research is needed to determine the cause of the differences in conditioned fear that we previously observed (as they were not observed in the current experiments).
我们之前的研究表明，雄性长 Evans 大鼠的低自愿酒精摄入量与高条件性恐惧之间存在关联。在此，我们研究了内源性阿片系统的差异是否可能是造成这些差异的原因。从出生后第 26 天至第 66 天，大鼠接受为期 6 周的慢性间歇性 20%酒精（体积/体积）或仅饮水。根据酒精摄入最后 2 周的摄入量，将酒精摄入组大鼠分为高饮用量组（>2.5 g/kg/24 小时）或低饮用量组（<2 g/kg/24 小时）。然后在恐惧条件反射训练前，给大鼠注射优先的 μ 阿片受体拮抗剂纳曲酮（1 mg/kg，皮下注射）或选择性 κ 阿片受体拮抗剂 LY2456302（10 mg/kg，皮下注射），并在 2 天后测试条件性恐惧。训练前注射纳曲酮增加了训练和测试期间杠杆按压的条件性抑制，高饮酒者与低饮酒者之间或仅饮水组与酒精摄入组之间（按饮酒水平平均）无差异。在任何比较中，LY2456302 对条件性恐惧均无影响。我们还发现高饮酒者与低饮酒者之间无差异，且先前酒精摄入（按饮酒水平平均）对条件性恐惧无可靠影响。我们的实验重复并扩展了先前的证明，即优先的 MOR 拮抗剂可以通过将杠杆按压的条件性抑制作为恐惧测量方法来增加恐惧学习。然而，需要进一步的研究来确定我们之前观察到的条件性恐惧差异的原因（因为在当前实验中未观察到）。
