Renicker Micah D, Cysewski Nicholas, Palmer Samuel, Nakonechnyy Dmytro, Keef Andrew, Thomas Morgan, Magori Krisztian, Daberkow David P
Department of Biology, Eastern Washington University, Cheney, WA, United States.
Front Behav Neurosci. 2018 May 28;12:105. doi: 10.3389/fnbeh.2018.00105. eCollection 2018.
Oxytocin treatment reduces signs of long-term emotional stress after exposure to trauma; however, little is known about the potential protective effects of oxytocin treatment on behavioral and physiological changes associated with extreme stress exposure. The objective of this study was to investigate oxytocin treatment as a prophylactic measure against rat signs of fear. Two separate experiments were conducted in which the time of intranasal oxytocin administration differed. Intranasal oxytocin (1.0 μg/kg) was administered 5 min after daily exposure to foot shock in Experiment #1 and 1 h before foot shock in Experiment #2. In Experiment #1, possible massage-evoked oxytocin release (5 min after foot shock) was also investigated. In both experiments, a contextual fear conditioning procedure was employed in which stress was induced via inescapable foot shock (3 days, 40 shocks/day, 8 mA/shock) in a fear conditioning chamber. Male Sprague-Dawley rats ( = 24) were divided into four groups ( = 6, per group) for each experiment. Experiment #1 groups: (intranasal saline and no foot shock); (intranasal saline 5 min after foot shock); (massage-like stroking and intranasal saline 5 min after foot shock); (intranasal oxytocin 5 min after foot shock). Experiment #2 groups: (intranasal saline and no foot shock); (intranasal saline 1 h before foot shock); (intranasal oxytocin and no foot shock); (intranasal oxytocin 1 h before foot shock). One week after fear conditioning (and other treatments), rats were independently evaluated for behavioral signs of fear. Two weeks after conditioning, physiological signs of fear were also assessed (Experiment #1). Relative to controls, rats treated with intranasal oxytocin 5 min after daily foot shock sessions exhibited significantly less immobility upon re-exposure to the shock chamber and attenuated physiological responses related to fear (e.g., elevated heart rate and blood pressure). Furthermore, intranasal oxytocin treatment given 1 h before daily foot shock sessions significantly decreased immobility and defecation upon re-exposure to the shock chamber, relative to controls. The results of this study suggest that prophylactic intranasal oxytocin, administered contemporaneously with aversive stimuli, mitigates behavioral and physiological responses associated with traumatic stress.
催产素治疗可减轻创伤暴露后的长期情绪应激迹象；然而，关于催产素治疗对与极端应激暴露相关的行为和生理变化的潜在保护作用，人们知之甚少。本研究的目的是调查催产素治疗作为预防大鼠恐惧迹象的措施。进行了两个独立的实验，其中鼻内给予催产素的时间不同。在实验1中，每天暴露于足部电击后5分钟给予鼻内催产素（1.0μg/kg），在实验2中，在足部电击前1小时给予。在实验1中，还研究了可能由按摩引起的催产素释放（足部电击后5分钟）。在两个实验中，均采用情境恐惧条件反射程序，其中在恐惧条件反射箱中通过不可逃避的足部电击（3天，每天40次电击，8mA/次电击）诱导应激。将雄性Sprague-Dawley大鼠（n = 24）分为四组（每组n = 6）进行每个实验。实验1的分组：A组（鼻内给予生理盐水且无足部电击）；B组（足部电击后5分钟鼻内给予生理盐水）；C组（类似按摩的抚摸且足部电击后5分钟鼻内给予生理盐水）；D组（足部电击后5分钟鼻内给予催产素）。实验2的分组：A组（鼻内给予生理盐水且无足部电击）；B组（足部电击前1小时鼻内给予生理盐水）；C组（鼻内给予催产素且无足部电击）；D组（足部电击前1小时鼻内给予催产素）。恐惧条件反射（和其他处理）一周后，对大鼠的恐惧行为迹象进行独立评估。条件反射两周后，还评估了恐惧的生理迹象（实验1）。与对照组相比，每天足部电击后5分钟接受鼻内催产素治疗的大鼠在再次暴露于电击箱时表现出明显更少的不动行为，并减弱了与恐惧相关的生理反应（例如，心率和血压升高）。此外，与对照组相比，每天足部电击前1小时给予鼻内催产素治疗可显著降低再次暴露于电击箱时的不动行为和排便。本研究结果表明，与厌恶刺激同时给予预防性鼻内催产素可减轻与创伤性应激相关的行为和生理反应。
