Ghaw Ashley, Chunduri Alisha, Chang Arnold, Ortiz Richard J, Kozlowska Milena, Kulkarni Praveen P, Ferris Craig F
Center for Translational Neuroimaging, Northeastern University, Boston, MA 02115, USA.
Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, NM 88003, USA.
Brain Commun. 2024 Jun 4;6(3):fcae194. doi: 10.1093/braincomms/fcae194. eCollection 2024.
Lysergic acid diethylamide is a hallucinogen with complex neurobiological and behavioural effects. This is the first study to use MRI to follow functional changes in brain activity in response to different doses of lysergic acid diethylamide in fully awake, drug-naive rats. We hypothesized that lysergic acid diethylamide would show a dose-dependent increase in activity in the prefrontal cortex and thalamus while decreasing hippocampal activity. Female and male rats were given intraperitoneal injections of vehicle or lysergic acid diethylamide in doses of 10 or 100 g/kg while fully awake during the imaging session. Changes in blood oxygen level-dependent signal were recorded over a 30-min window. Approximately 45-min post-injection data for resting-state functional connectivity were collected. All data were registered to rat 3D MRI atlas with 173 brain regions providing site-specific increases and decreases in global brain activity and changes in functional connectivity. Treatment with lysergic acid diethylamide resulted in a significant dose-dependent increase in negative blood oxygen level-dependent signal. The areas most affected were the primary olfactory system, prefrontal cortex, thalamus and hippocampus. This was observed in both the number of voxels affected in these brains regions and the changes in blood oxygen level-dependent signal over time. However, there was a significant increase in functional connectivity between the thalamus and somatosensory cortex and the cerebellar nuclei and the surrounding brainstem areas. Contrary to our hypothesis, there was an acute dose-dependent increase in negative blood oxygen level-dependent signal that can be interpreted as a decrease in brain activity, a finding that agrees with much of the behavioural data from preclinical studies. The enhanced connectivity between thalamus and sensorimotor cortices is consistent with the human literature looking at lysergic acid diethylamide treatments in healthy human volunteers. The unexpected finding that lysergic acid diethylamide enhances connectivity to the cerebellar nuclei raises an interesting question concerning the role of this brain region in the psychotomimetic effects of hallucinogens.
麦角酸二乙酰胺是一种具有复杂神经生物学和行为效应的致幻剂。这是第一项使用磁共振成像（MRI）来追踪完全清醒、未接触过药物的大鼠在不同剂量麦角酸二乙酰胺作用下大脑活动功能变化的研究。我们假设麦角酸二乙酰胺会使前额叶皮质和丘脑的活动呈剂量依赖性增加，同时降低海马体的活动。在成像过程中，雌雄大鼠均在完全清醒状态下接受腹腔注射溶剂或剂量为10或100 μg/kg的麦角酸二乙酰胺。在30分钟的时间段内记录血氧水平依赖信号的变化。注射后约45分钟收集静息态功能连接的数据。所有数据都被注册到具有173个脑区的大鼠三维MRI图谱中，该图谱提供了全脑活动中特定部位的增加和减少以及功能连接的变化。麦角酸二乙酰胺治疗导致负性血氧水平依赖信号显著呈剂量依赖性增加。受影响最严重的区域是初级嗅觉系统、前额叶皮质、丘脑和海马体。这在这些脑区受影响的体素数量以及血氧水平依赖信号随时间的变化中都有观察到。然而，丘脑与体感皮质以及小脑核与周围脑干区域之间的功能连接有显著增加。与我们的假设相反，负性血氧水平依赖信号出现急性剂量依赖性增加，这可以解释为大脑活动的减少，这一发现与临床前研究的许多行为数据一致。丘脑与感觉运动皮质之间增强的连接与观察健康人类志愿者麦角酸二乙酰胺治疗的人类文献一致。麦角酸二乙酰胺增强与小脑核的连接这一意外发现，引发了一个关于该脑区在致幻剂拟精神病效应中作用的有趣问题。
