Bodnar R J, Mann P E, Stone E A
Pharmacol Biochem Behav. 1985 Nov;23(5):749-52. doi: 10.1016/0091-3057(85)90066-8.
Like other stress responses, cold-water swim (CWS) analgesia can be altered by changes in norepinephrine (NE) availability. While clonidine pretreatment potentiates CWS analgesia, lesions placed in the noradrenergic locus coeruleus reduce this response. Desipramine (DMI) can alter both the availability and receptor function of catecholamines, particularly NE: while both acute and chronic DMI treatments decrease NE reuptake, subsensitivity of beta-adrenergic receptors occurs only after chronic DMI treatment. The present study examined whether acute and chronic DMI treatments differentially alter CWS analgesia as measured by the jump test, CWS hypothermia and basal jump thresholds. The first experiment determined that pretreatment at either 24, 5 and 1 hr or only at 1 hr with DMI doses of 20 and 5 but not 1 mg/kg potentiated CWS analgesia. The second experiment found that chronic DMI pretreatment at a dose of 10 mg/kg administered twice daily over seven days failed to alter CWS analgesia at 1, 24, 48 or 72 hr thereafter. Neither CWS hypothermia nor basal jump thresholds were affected by the acute or chronic DMI injection regimens. The selective potentiation of CWS analgesia by acute DMI pretreatment is discussed in terms of the differential actions of acute and chronic injection regimens upon NE availability, receptor function, and adaptation processes.
与其他应激反应一样，冷水游泳（CWS）镇痛作用可因去甲肾上腺素（NE）可用性的变化而改变。虽然可乐定预处理可增强CWS镇痛作用，但损毁去甲肾上腺素能蓝斑核会减弱这种反应。地昔帕明（DMI）可改变儿茶酚胺，尤其是NE的可用性和受体功能：急性和慢性DMI治疗均会降低NE的再摄取，但β-肾上腺素能受体的敏感性降低仅在慢性DMI治疗后出现。本研究通过跳跃试验、CWS体温过低和基础跳跃阈值来检测急性和慢性DMI治疗是否会对CWS镇痛产生不同影响。第一个实验确定，以20 mg/kg和5 mg/kg而非1 mg/kg的DMI剂量在24小时、5小时和1小时或仅在1小时进行预处理可增强CWS镇痛作用。第二个实验发现，在七天内每天两次给予10 mg/kg剂量的慢性DMI预处理在随后的1小时、24小时、48小时或72小时均未改变CWS镇痛作用。急性或慢性DMI注射方案均未影响CWS体温过低或基础跳跃阈值。根据急性和慢性注射方案对NE可用性、受体功能和适应过程的不同作用，讨论了急性DMI预处理对CWS镇痛的选择性增强作用。
