Neural encoding of psychomotor activation in the nucleus accumbens core, but not the shell, requires cannabinoid receptor signaling.
Neural encoding of psychomotor activation in the nucleus accumbens core, but not the shell, requires cannabinoid receptor signaling.
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DOI：
10.1523/jneurosci.5335-09.2010
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发表时间：
2010-04-07
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影响因子：
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通讯作者：
Cheer JF
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文献类型：
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作者：
Morra JT;Glick SD;Cheer JF
本研究旨在进一步阐明内源性大麻素信号在甲基苯丙胺诱导的精神兴奋中的作用。用双侧颅内微量注射大麻素CB 1受体拮抗剂利莫那班（1 μg; 1 μl）或AM 251（1 μg; 1 μ l）或溶媒（1 μl）处理大鼠，然后静脉注射甲基苯丙胺（3 mg/kg）。拮抗剂预处理的核心，但不壳，衰减甲基苯丙胺诱导的刻板，而在任何大脑区域的治疗药物诱导的运动没有影响。在一个平行的实验中，我们记录了多个单单位的行为大鼠的延髓核静脉注射利莫那班（0.3毫克/公斤）或车辆，然后用甲基苯丙胺（0.01，0.1，1，3毫克/公斤;累积剂量）。我们观察到强大的，阶段性的变化，神经元放电的时间锁定的发病甲基苯丙胺诱导的运动和刻板。在核心中观察到刻板印象编码，并通过CB 1受体拮抗作用减弱，而运动相关性在所有的神经元中均匀观察到，并且不受利莫那班的影响。心理激活编码主要由假定的快速尖峰中间神经元表达。因此，我们建议，内源性大麻素调制的精神活动优先驱动的CB 1受体依赖性的中间神经元的活动，在神经核的核心。
The current study aimed to further elucidate the role of endocannabinoid signaling in methamphetamine-induced psychomotor activation. Rats were treated with bilateral, intracranial microinjections of the cannabinoid CB1 receptor antagonists rimonabant (1 μg; 1 μl) or AM251 (1 μg; 1 μl), or vehicle (1 μl), followed by intravenous methamphetamine (3 mg/kg). Antagonist pretreatment in the nucleus accumbens core, but not shell, attenuated methamphetamine-induced stereotypy, while treatment in either brain region had no effect on drug-induced locomotion. In a parallel experiment, we recorded multiple single-units in the nucleus accumbens of behaving rats treated with intravenous rimonabant (0.3 mg/kg) or vehicle, followed by methamphetamine (0.01, 0.1, 1, 3 mg/kg; cumulative dosing). We observed robust, phasic changes in neuronal firing time-locked to the onset of methamphetamine-induced locomotion and stereotypy. Stereotypy encoding was observed in the core and was attenuated by CB1 receptor antagonism, while locomotor correlates were observed uniformly across the accumbens and were not affected by rimonabant. Psychomotor activation encoding was expressed predominantly by putative fast-spiking interneurons. We therefore propose that endocannabinoid modulation of psychomotor activation is preferentially driven by CB1 receptor-dependent interneuron activity in the nucleus accumbens core.