Baracz Sarah J, Everett Nicholas A, McGregor Iain S, Cornish Jennifer L
Department of Psychology, Macquarie University, Australia.
School of Psychology, University of Sydney, Australia.
Addict Biol. 2016 Mar;21(2):316-25. doi: 10.1111/adb.12198. Epub 2014 Nov 16.
The psychostimulant methamphetamine (METH) is an addictive illicit drug. Systemic administration of the neuropeptide oxytocin modulates METH-related reward and METH-seeking behaviour. Recent findings demonstrated a reduction in METH-induced reward by oxytocin administration into the nucleus accumbens (NAc) core. It is not known, however, if oxytocin acts in this region to reduce relapse to METH-seeking behaviour. Using the drug reinstatement paradigm in rats experienced at METH self-administration, we aimed to determine whether oxytocin pre-treatment within the NAc core would reduce relapse to METH use and if this could be reversed by the co-administration of the oxytocin receptor (OTR) antagonist desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT. Male Sprague-Dawley rats underwent surgery to implant an intravenous jugular vein catheter and bilateral microinjection cannulae in the NAc core. Rats were then trained to self-administer intravenous METH (0.1 mg/kg/infusion) by lever press during 2-hour fixed ratio 1 scheduled sessions for 20 days. Following extinction of lever press activity, the effect of microinjecting saline, oxytocin (0.5 pmol, 1.5 pmol, 4.5 pmol) or co-administration of oxytocin (1.5 pmol) and desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT (1 nmol, 3 nmol) in the NAc core (500 nl/side) was examined on METH-primed (1 mg/kg, i.p.) reinstatement of drug-seeking behaviour. Our results showed oxytocin directly administered into the NAc core decreased METH-primed reinstatement in a dose-dependent manner. Co-administration of the selective OTR antagonist did not specifically reverse the inhibitory effects of oxytocin on METH priming, suggesting mediation by receptors other than the OTR. These findings highlight an important modulatory effect of oxytocin in the NAc core on relapse to METH seeking.
精神兴奋剂甲基苯丙胺（METH）是一种成瘾性非法药物。神经肽催产素的全身给药可调节与METH相关的奖赏及觅药行为。最近的研究结果表明，向伏隔核（NAc）核心注射催产素可降低METH诱导的奖赏。然而，催产素是否在该区域发挥作用以减少复发性觅药行为尚不清楚。我们利用METH自我给药实验大鼠的药物复吸范式，旨在确定NAc核心内的催产素预处理是否会减少METH使用的复发，以及这是否可通过共同给予催产素受体（OTR）拮抗剂去甘氨酰胺、d（CH2）5[D-酪氨酸2，苏氨酸4]催产素（desGly-NH2,d(CH2)5[D-Tyr2,Thr4]OVT）来逆转。雄性Sprague-Dawley大鼠接受手术，植入颈静脉导管和双侧NAc核心微量注射套管。然后训练大鼠在2小时固定比率1的给药时段内通过按压杠杆自我静脉注射METH（0.1mg/kg/次），持续20天。在杠杆按压活动消退后，研究向NAc核心（每侧500nl）微量注射生理盐水、催产素（0.5pmol、1.5pmol、4.5pmol）或共同给予催产素（1.5pmol）和去甘氨酰胺、d（CH2）5[D-酪氨酸2，苏氨酸4]催产素（1nmol、3nmol）对METH激发（1mg/kg，腹腔注射）的觅药行为复吸的影响。我们的结果表明，直接注射到NAc核心的催产素以剂量依赖的方式降低了METH激发的复吸。选择性OTR拮抗剂的共同给药并未特异性逆转催产素对METH激发的抑制作用，提示其作用是由OTR以外的受体介导的。这些发现突出了催产素在NAc核心对复发性觅药行为的重要调节作用。
