Stivers J A, Kaltwasser M T, Hill P S, Hruby V J, Crawley J N
Clinical Neuroscience Branch, National Institute of Mental Health, Bethesda, MD 20892.
Peptides. 1988;9 Suppl 1:223-31. doi: 10.1016/0196-9781(88)90248-3.
Bilateral microinjection of oxytocin (OXY) into the ventral tegmental area (VTA) of rat brain produced a significant increase in grooming behaviors at doses from 100 pg to 400 ng. Sites in the caudal region of the VTA were sensitive to lower doses of OXY than sites in the rostral region of the VTA. The time course of action of OXY in the grooming paradigm indicated onset beginning immediately after injection, and termination at 60-75 minutes after injection. Comparison of OXY-induced grooming in male, female, and ovariectomized, estrogen-treated female rats showed no differences in potency for OXY among these groups, suggesting that the grooming effects of OXY are not regulated by sex steroids. Analysis of locomotor activity in rats microinjected with OXY 200 ng bilaterally into the caudal VTA revealed that OXY had no effect on ambulatory locomotion, suggesting that this peptide may activate neurons within the VTA which mediate grooming but not locomotion. The OXY receptor antagonist, [Pen1, pMePhe2, Thr4, Orn8]-OT, blocked OXY-induced grooming when both were simultaneously microinjected into the VTA. The dopamine D-2 receptor antagonist, haloperidol, and the D-1 receptor antagonist, SCH 23390, when microinjected into the VTA five minutes before microinjection of OXY into the VTA, did not block OXY-induced grooming, suggesting that OXY is not working through a dopamine autoreceptor on the VTA neurons. Systemic pretreatment with haloperidol and SCH 23390 effectively blocked grooming induced by OXY in the VTA, suggesting that OXY is directly stimulating OXY receptors on VTA neurons to release dopamine at postsynaptic sites regulating grooming behaviors.
向大鼠脑腹侧被盖区(VTA)双侧微量注射催产素(OXY),剂量在100皮克至400纳克时,梳理行为显著增加。VTA尾侧区域的位点比VTA头侧区域的位点对更低剂量的OXY更敏感。在梳理范式中,OXY的作用时间进程表明,注射后立即开始起效,注射后60 - 75分钟作用终止。对雄性、雌性以及卵巢切除并用雌激素处理的雌性大鼠中OXY诱导的梳理行为进行比较,结果显示这些组中OXY的效力没有差异,这表明OXY的梳理作用不受性类固醇调节。对双侧尾侧VTA微量注射200纳克OXY的大鼠的运动活动进行分析发现,OXY对行走运动没有影响,这表明该肽可能激活VTA内介导梳理行为而非运动的神经元。当OXY受体拮抗剂[Pen1,pMePhe2,Thr4,Orn8]-OT与OXY同时微量注射到VTA中时,可阻断OXY诱导的梳理行为。多巴胺D - 2受体拮抗剂氟哌啶醇和D - 1受体拮抗剂SCH 23390,在向VTA微量注射OXY前五分钟微量注射到VTA中时,并未阻断OXY诱导的梳理行为,这表明OXY并非通过VTA神经元上的多巴胺自身受体起作用。用氟哌啶醇和SCH 23390进行全身预处理可有效阻断VTA中OXY诱导的梳理行为,这表明OXY直接刺激VTA神经元上的OXY受体,在调节梳理行为的突触后位点释放多巴胺。