Regulatory actions of therapeutic drugs for affective disorders on circadian rhythm of rat behviors.

1)锂、氯丙咪嗪、丙咪嗪和促甲状腺激素释放激素的作用：雄性SD大鼠长期侧脑室插管，双眼摘除眼球，放入恒光下。自由活动3~5周后，在氟烷麻醉下，经硅胶管连接微型渗透泵(阿尔采特，2002年)，经脑室持续滴注药液(流速0.5g/h；L/h)。在EAT大鼠中，每隔10分钟同时测量行走、饮水和进食。自由运行昼夜节律的变化被计算为&lt；Delta；&lt；tau&gt；(植入后减去植入前&lt；tau&gt；)。0.35-567.5 NM/kg/h静脉滴注CMP(n=10)-0.02h(平均值为-0.12h~+0.07h)，与剂量的相关系数为-0.84(P&lt；0.001)。0.3…静脉滴注6~828.7 nm/kg/h以上的IMP(n=10)引起+0.01±0.01h，r=-0.56(&lt；0.05)。5.7-6.6 NM/kg/h静脉滴注TRH(n=5)产生0.00-0.01h(范围-0.03-+0.06h)的&lt；Delta&gt；&lt；tau&gt；36只大鼠以0.2~17.9 mg/kg/h的速度静脉滴注氯化锂。10只大鼠在锂中毒速率大于6&lt；m/kg/h时死亡，其余26只大鼠的氯化锂生成量为+0.07~+0.36，r为+0.24(Ns)。另一方面，皮下注射18.6-66.4；M/kg/h氯化锂(n=4)引起+0.12&lt；+！-&gt；0.04h(范围0.00-+0.20h)。作为对照，L微量静脉滴注生理盐水0.5h/h(n=4)，产生+0.04h~+0.08h。综上所述，在较高剂量下，CMP和IMP缩短了Lt；tau&gt；，而LiCl2)延长了Lt；tau&gt；2)昼夜节律到明暗周期的夹带范围和锂的影响。为了确定SD大鼠昼夜行为节律的夹带范围，从2 4h周期(LD 12：12)开始，以2 0min步长逐渐缩短或延长LD周期(n=10)，在此期间，L周期长度始终等于D周期长度，光照强度为10 0lux。摄取节律的夹带上限为27h~40m~29h，动态节律为28h~29h~20m。在较长的LD周期中，行为节律被相位提前到LD周期。在暴露于LD 14：14期间，经微型渗透泵以22.5微米/小时的速度皮下注射LiCl2周，并未改变夹带程度和昼夜节律的高级阶段。睡眠、行走、饮水、进食的携带下限为23h~20m。在暴露于这个LD周期期间，行为节律被延迟到LD周期。较少

1) Effects of lithium (LiCl), clomipramine (CMP), imipramine (IMP), and thyrotropin releasing hormone (TRH): Male Sprague-Dawley rats chronically implanted with a cannula in the lateral ventricle were bilaterally eye-enucleated and released into constant light. After 3-5 weeks of free-running, the rats received a 2-week continuous intraventricular (ivt) infusion of a drug solution (flow rate, 0.5 <micro> l/h) via a silicone tubing connected with a mini-osmotic pump (Alzet, #2002) implanted subcutaneously under halothane anesthesia. In eat rat, ambulation, drinking and eating were simultaneously measured at 10-min intervals. A change in free-running circadian period ( <tau> ) was calculated as <delta> <tau> (post-implantation <tau> minus pre-implantation <tau> ). 0.35-567.5 nM/kg/h ivt infusions of CMP (n=10) produced <delta> <tau> of -0.02 <+!-> 0.02 h (mean <+!-> SE) ranging from -0.12 h to +0.07; the correlation coefficient (r) between <delta> <tau> and doses was -0.84 (P<0.001). 0.3 … More 6-828.7 nM/kg/h ivt infusions of IMP (n=10) caused <delta> <tau> of +0.01 + 0.01 h ranging from -0.05 h to +0.09; the r was -0.56 (<0.05). 5.7 -6.6 nM/kg/h ivt infusions of TRH (n=5) produced <delta> <tau> of 0.00 <+!-> 0.01 h (range, -0.03 to +0.06 h). LiCl was ivt infused at the rates of 0.2-17.9 <micro> M/kg/h in 36 rats. Ten rats died from Li intoxication when the rate was over 6 <micro> M/kg/h. In the remaining 26 rats, LiCl produced <delta> <tau> of +0.07 <+!-> 0.02 h ranging from -0.07 h to +0.36; the r was +0.24 (ns). On the other hand, 18.6 -66.4 <micro> M/kg/h subcutaneous infusions of LiCl (n=4) caused <delta> <tau> of +0.12 <+!-> 0.04 h (range, 0.00 to +0.20 h). As a control, 0.5 <micro> l/h ivt infusion of physiological saline (n=4) produced <delta> <tau> ranging from +0.04 h to +0.08. In conclusion, CMP and IMP shortens <tau> at higher doses whereas LiCl prolongs it.2) The range of entrainment of circadian rhythm to light-dark (LD) cycle and the effect of lithium. In order to determine the range of entrainment of circadian behavioral rhythms of Sprague-Dawley rats, the LD cycle was shortened (n=10) or lengthened (n=10) gradually by 20-min steps from 24 h period (LD 12:12), during which the L period length always equaled the D period length and the light intensity was 100 lux. The upper limit of entrainment was between 27 h 40 m and 29 h for drinking rhythm, and between 28 h 20 m and 29 h 20 m for ambulatory rhythm. During exposure to the longer LD periods, the behavioral rhythms were phase-advanced to the LD cycle. During exposure to LD 14:14, 2-week subcutaneous infusion of LiCl at the rate of 22.5 <micro> M/h via a mini-osmotic pump did not alter the degree of entrainment and the advanced phase of circadian rhythms. The lower limit of entrainment was 23 h 20 m for sleep, ambulation, drinking and eating. During exposure to this LD cycle, the behavioral rhythms was phase-delayed to the LD cycle. Less