Ferris Craig F, Stolberg Tara, Kulkarni Praveen, Murugavel Murali, Blanchard Robert, Blanchard D Caroline, Febo Marcelo, Brevard Mathew, Simon Neal G
Center for Translational NeuroImaging, Northeastern University, Boston, Massachusetts, USA.
BMC Neurosci. 2008 Nov 13;9:111. doi: 10.1186/1471-2202-9-111.
With the advent of functional magnetic resonance imaging (fMRI) in awake animals it is possible to resolve patterns of neuronal activity across the entire brain with high spatial and temporal resolution. Synchronized changes in neuronal activity across multiple brain areas can be viewed as functional neuroanatomical circuits coordinating the thoughts, memories and emotions for particular behaviors. To this end, fMRI in conscious rats combined with 3D computational analysis was used to identifying the putative distributed neural circuit involved in aggressive motivation and how this circuit is affected by drugs that block aggressive behavior.
To trigger aggressive motivation, male rats were presented with their female cage mate plus a novel male intruder in the bore of the magnet during image acquisition. As expected, brain areas previously identified as critical in the organization and expression of aggressive behavior were activated, e.g., lateral hypothalamus, medial basal amygdala. Unexpected was the intense activation of the forebrain cortex and anterior thalamic nuclei. Oral administration of a selective vasopressin V1a receptor antagonist SRX251 or the selective serotonin reuptake inhibitor fluoxetine, drugs that block aggressive behavior, both caused a general suppression of the distributed neural circuit involved in aggressive motivation. However, the effect of SRX251, but not fluoxetine, was specific to aggression as brain activation in response to a novel sexually receptive female was unaffected.
The putative neural circuit of aggressive motivation identified with fMRI includes neural substrates contributing to emotional expression (i.e. cortical and medial amygdala, BNST, lateral hypothalamus), emotional experience (i.e. hippocampus, forebrain cortex, anterior cingulate, retrosplenial cortex) and the anterior thalamic nuclei that bridge the motor and cognitive components of aggressive responding. Drugs that block vasopressin neurotransmission or enhance serotonin activity suppress activity in this putative neural circuit of aggressive motivation, particularly the anterior thalamic nuclei.
随着清醒动物功能磁共振成像（fMRI）技术的出现，现在有可能以高空间和时间分辨率解析整个大脑的神经元活动模式。多个脑区神经元活动的同步变化可被视为协调特定行为的思想、记忆和情感的功能性神经解剖回路。为此，采用清醒大鼠的fMRI结合三维计算分析来确定参与攻击动机的假定分布式神经回路，以及该回路如何受到阻断攻击行为的药物的影响。
为了激发攻击动机，在图像采集期间，将雄性大鼠与其雌性笼伴以及一只陌生雄性入侵者置于磁体孔内。正如预期的那样，先前确定在攻击行为的组织和表达中起关键作用的脑区被激活，例如外侧下丘脑、内侧基底杏仁核。出乎意料的是，前脑皮质和前丘脑核也被强烈激活。口服选择性血管加压素V1a受体拮抗剂SRX251或选择性5-羟色胺再摄取抑制剂氟西汀，这两种阻断攻击行为的药物，均导致参与攻击动机的分布式神经回路普遍受到抑制。然而，SRX251的作用具有攻击性特异性，而氟西汀则不然，因为对新的性接受雌性的脑激活不受影响。
通过fMRI确定的攻击动机假定神经回路包括有助于情绪表达的神经基质（即皮质和内侧杏仁核、终纹床核、外侧下丘脑）、情绪体验（即海马体、前脑皮质、前扣带回、压后皮质）以及连接攻击反应的运动和认知成分的前丘脑核。阻断血管加压素神经传递或增强5-羟色胺活性的药物会抑制这个假定的攻击动机神经回路的活动，特别是前丘脑核。
