Stress Sensitization of ethanol withdrawal-induced reduction in social interaction:: Inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist
Stress Sensitization of ethanol withdrawal-induced reduction in social interaction:: Inhibition by CRF-1 and benzodiazepine receptor antagonists and a 5-HT1A-receptor agonist
复制标题
DOI：
10.1038/sj.npp.1300282
复制
发表时间：
2004-03-01
影响因子：
7.6
通讯作者：
Overstreet, DH
中科院分区：
文献类型：
--
作者：
Breese, GR;Knapp, DJ;Overstreet, DH
反复从慢性酒精中戒断使戒断引起的社会交往行为减少敏感化。这项研究确定了压力是否可以代替反复的戒断，以促进戒断引起的焦虑样行为。当两个1小时的约束压力期间，在1周的时间间隔，以控制饮食喂养的大鼠，社会互动减少后退出随后的5天暴露于乙醇饮食。无论是单独接触乙醇还是单独接触三种束缚压力都没有改变这种焦虑程度。此外，反复强调单一撤回大鼠继续表现出减少社会互动16天后，退出后，从再暴露于5天的慢性乙醇，与持久的适应多重压力/撤退协议。每周给予皮质酮代替应激在从单次慢性乙醇暴露中戒断时没有引起社会交往的显著变化，表明皮质激素释放不是戒断期间应激诱导的焦虑样行为减少的原因。在多次戒断方案中，在P大鼠自愿饮酒戒断期间施加的应激充分促进了乙醇饮酒，从而导致社交互动的减少。在每次应激前给予CRF-I受体拮抗剂、苯二氮卓类受体拮抗剂或S-HT 1A受体激动剂可最大限度地降低戒断诱导的焦虑样行为减少的敏感性。由于这些药理学后果的诱导焦虑样行为后的压力/退出协议是像以前看到的，当这些药物治疗之前，多次退出，提供的证据表明，反复强调和多次退出敏感的退出减少社会互动相似的中央适应机制。
Repeated withdrawals from chronic ethanol sensitize the withdrawal-induced reduction in social interaction behaviors. This study determined whether stress might substitute for repeated withdrawals to facilitate withdrawal-induced anxiety-like behavior. When two 1-h periods of restraint stress were applied at 1-week intervals to rats fed control diet, social interaction was reduced upon withdrawal from a subsequent 5-day exposure to ethanol diet. Neither this ethanol exposure alone nor exposure to three restraint stresses alone altered this measure of anxiety. Further, the repeatedly stressed singly withdrawn rats continued to exhibit a reduction in social interaction 16 days later, upon withdrawal from re-exposure to 5 days of chronic ethanol, consistent with a persistent adaptation by the multiple-stress/withdrawal protocol. Weekly administration of corticosterone in place of stress induced no significant change in social interaction upon withdrawal from the single chronic ethanol exposure, indicative that corticoid release is not responsible for the stress-induced reduction in anxiety-like behavior during withdrawal, In the multiple-withdrawal protocol, stress applied during withdrawal from voluntary ethanol drinking by P-rats facilitated ethanol drinking sufficiently, to induce a withdrawal-induced reduction in social interaction. Administration of a CRF-I receptor antagonist, a benzodiazepine receptor antagonist, or a S-HT1A receptor agonist prior to each stress minimized sensitization of the withdrawal-induced reduction in anxiety-like behavior. Since these pharmacological consequences on the induction of anxiety-like behavior following the stress/withdrawal protocol are like those previously seen when these drug treatments were given prior to multiple withdrawals, evidence is provided that repeated stresses and multiple withdrawals sensitize the withdrawal reduction in social interaction by similar central adaptive mechanisms.