Marquez Paul, Bebawy David, Lelièvre Vincent, Coûté Anne-Claire, Evans Christopher J, Waschek James A, Lutfy Kabirullah
Department of Pharmaceutical Sciences, Western University of Health Sciences, Pomona, CA 91766, USA.
Psychopharmacology (Berl). 2009 Jun;204(3):457-63. doi: 10.1007/s00213-009-1476-9. Epub 2009 Feb 8.
The neuropeptide pituitary adenylyl cyclase-activating peptide (PACAP) and its receptors (PAC1 and VPAC2) are expressed in the ventral tegmental area and nucleus accumbens, raising the possibility that PACAP could be a potential modulator of the mesolimbic dopaminergic system.
The present study was designed to determine if PACAP plays a role in acute motor stimulatory and rewarding actions of morphine.
The effect of intracerebroventricular PACAP administration (0, 0.03, 0.3, 1.0, or 3.0 microg/3 microL) was studied on basal motor activity as well as on morphine (5 mg/kg)-stimulated motor activity. Motor stimulation and conditioned place preference (CPP) induced by morphine (5 or 10 mg/kg) were also determined in mice lacking PACAP and their wild-type controls.
Intracerebroventricular PACAP dose-dependently suppressed basal motor activity and PACAP-deficient mice exhibited higher basal motor activity than control mice, providing evidence that the action of endogenous PACAP on basal motor activity is inhibitory. Paradoxically, low doses of PACAP which did not alter basal motor activity were found to enhance the motor stimulatory action of morphine. Furthermore, morphine-induced motor stimulation was blunted in PACAP-deficient mice. Additionally, morphine-induced CPP following a single, but not repeated, alternate-day saline/morphine (10 mg/kg) conditioning was blunted in PACAP-deficient mice compared to their wild-type littermates/controls.
The present results suggest that endogenous PACAP, at low doses, positively modulates the acute motor stimulatory and rewarding actions of morphine.
神经肽垂体腺苷酸环化酶激活肽（PACAP）及其受体（PAC1和VPAC2）在腹侧被盖区和伏隔核中表达，这增加了PACAP可能是中脑边缘多巴胺能系统潜在调节剂的可能性。
本研究旨在确定PACAP是否在吗啡的急性运动刺激和奖赏作用中发挥作用。
研究了脑室内注射PACAP（0、0.03、0.3、1.0或3.0微克/3微升）对基础运动活动以及吗啡（5毫克/千克）刺激的运动活动的影响。还在缺乏PACAP的小鼠及其野生型对照中测定了吗啡（5或10毫克/千克）诱导的运动刺激和条件性位置偏爱（CPP）。
脑室内注射PACAP剂量依赖性地抑制基础运动活动，且缺乏PACAP的小鼠表现出比对照小鼠更高的基础运动活动，这证明内源性PACAP对基础运动活动的作用是抑制性的。矛盾的是，发现不改变基础运动活动的低剂量PACAP可增强吗啡的运动刺激作用。此外，缺乏PACAP的小鼠中吗啡诱导的运动刺激减弱。另外，与野生型同窝小鼠/对照相比，在缺乏PACAP的小鼠中，单次（而非重复的隔日）生理盐水/吗啡（10毫克/千克）条件反射后吗啡诱导的CPP减弱。
目前的结果表明，低剂量的内源性PACAP对吗啡的急性运动刺激和奖赏作用具有正向调节作用。
