Effects of systemic opioid receptor ligands on ethanol- and sucrose seeking and drinking in alcohol-preferring (P) and Long Evans rats.
Effects of systemic opioid receptor ligands on ethanol- and sucrose seeking and drinking in alcohol-preferring (P) and Long Evans rats.
复制标题
DOI：
10.1007/s00213-014-3571-9
复制
发表时间：
2014-11
影响因子：
3.4
通讯作者：
Czachowski, Cristine
中科院分区：
文献类型：
--
作者：
Henderson-Redmond, Angela;Czachowski, Cristine
内源性阿片类药物系统与调节乙醇 (EtOH) 的增强作用有关。纳曲酮 (NTX)（一种对 mu 受体具有浓度依赖性选择性的阿片拮抗剂）、纳曲吲哚 (NTI)（一种选择性 δ 受体拮抗剂）和 U50,488H（一种选择性 kappa 受体激动剂）在酒精偏好 (P) 和非选择性 (Long Evans (LE)) 大鼠中进行了检查，以确定它们是否对乙醇和蔗糖的寻求和消耗产生不同影响。使用吸管模型，用 2% 蔗糖或 10% EtOH 强化的大鼠注射载体和 NTI（2.5、5.0 或 10.0 mg/kg）、U50（2.5、5.0 或 10.0 mg/kg）、低剂量 NTX（0.1、0.3 或 1.0 mg/kg）或高剂量 NTX （1.0、3.0 或 10.0 毫克/千克）。评估随后的摄入（完成）或杠杆反应（寻求）。总体而言，NTI、U50 和 NTX 减弱了蔗糖和 EtOH 的摄入和反应，EtOH 强化的 P 大鼠对 NTI 对摄入和寻求的影响最敏感。 U50 治疗减少了 P 和 LE 大鼠的摄入和寻找，但没有选择性地减少任一系的 EtOH 摄入或寻找。 P 大鼠比 LE 大鼠对较低剂量的 NTX 更敏感，并且这些剂量比蔗糖更有选择性地减弱对 EtOH 的反应。较高剂量的 NTX 抑制了跨线和强化剂的摄入和反应。这些结果表明，对阿片受体有选择性的药物可能是良好的药物治疗靶点，特别是对于那些具有更多乙醇偏好/摄入的潜在遗传倾向的患者。
The endogenous opioid system has been implicated in mediating the reinforcing effects of ethanol (EtOH). Naltrexone (NTX), an opioid antagonist with concentration-dependent selectivity for the mu receptor, naltrindole (NTI), a selective delta receptor antagonist, and U50,488H, a selective kappa receptor agonist were examined in both alcohol-preferring (P) and nonselected (Long Evans (LE)) rats to determine whether they differentially affected the seeking and consumption of EtOH and sucrose. Using the sipper-tube model, rats reinforced with either 2 % sucrose or 10 % EtOH were injected with vehicle and either NTI (2.5, 5.0, or 10.0 mg/ kg), U50 (2.5, 5.0, or 10.0 mg/kg), low-dose NTX (0.1, 0.3, or 1.0 mg/kg), or high-dose NTX (1.0, 3.0, or 10.0 mg/kg). Subsequent intakes (consummatory) or lever responses (seeking) were assessed. Overall, NTI, U50, and NTX attenuated intake and responding for sucrose and EtOH, with EtOH-reinforced P rats being the most sensitive to the effects of NTI on intake and seeking. U50 treatment decreased intake and seeking in both P and LE rats but did not selectively reduce EtOH intake or seeking in either line. P rats were more sensitive than LE rats to lower doses of NTX, and these doses more selectively attenuated responding for EtOH than sucrose. Higher doses of NTX suppressed intake and responding across both lines and reinforcers. These results suggest that drugs selective for the opioid receptors may be good pharmacotherapeutic targets, particularly in those with an underlying genetic predisposition for greater EtOH preference/intake.
登录
查看更多内容
影响因子：
5
作者：
BALSKUBIK, R;SHIPPENBERG, TS;HERZ, A
通讯作者：
HERZ, A
影响因子：
3.4
作者：
BALSKUBIK, R;HERZ, A;SHIPPENBERG, TS
通讯作者：
SHIPPENBERG, TS
影响因子：
10.6
作者：
Krishnan-Sarin, Suchitra;Krystal, John H.;O'Malley, Stephanie S.
通讯作者：
O'Malley, Stephanie S.
影响因子：
5
作者：
CHILDERS, SR;CREESE, I;SNYDER, SH
通讯作者：
SNYDER, SH
DOI：
10.1124/jpet.301.3.993
发表时间：
2002-06-01
影响因子：
3.5
作者：
Cosgrove, KP;Carroll, ME
通讯作者：
Carroll, ME