Moises H C
Department of Physiology, University of Michigan, Ann Arbor 48109.
Brain Res. 1987 Oct 13;423(1-2):149-61. doi: 10.1016/0006-8993(87)90835-3.
Inhibitory responses of rat cerebellar Purkinje cells to locus coeruleus (LC) stimulation and iontophoresis of norepinephrine (NE) were examined before and after administration of morphine to determine whether the inhibitory modulation of NE release by opiates results in a functional impairment in noradrenergic synaptic action. Administration of morphine systemically (0.2-1.2 mg/kg, i.v.) or by iontophoresis reduced inhibitions in Purkinje firing elicited by LC stimulation without affecting depressions in activity induced by postsynaptic applications of NE. This antagonistic effect of morphine on LC-induced inhibition was reversed or prevented by naloxone and mimicked by administration of levorphanol but not dextrorphan. Morphine increased the excitatory response of Purkinje cells to monosynaptic input from the parallel fibers, whereas it blocked gamma-aminobutyric acid-induced inhibitions in firing via a non-opiate receptor-mediated mechanism. These results demonstrate that morphine interferes with synaptic inhibition derived from the LC and suggest that this may occur via activation of presynaptic opiate receptors residing on noradrenergic nerve terminals.
在给予吗啡前后，检测大鼠小脑浦肯野细胞对蓝斑（LC）刺激和去甲肾上腺素（NE）离子透入的抑制反应，以确定阿片类药物对NE释放的抑制性调节是否会导致去甲肾上腺素能突触作用的功能损害。全身给予吗啡（0.2 - 1.2毫克/千克，静脉注射）或通过离子透入给药，可减少LC刺激引起的浦肯野细胞放电抑制，而不影响突触后应用NE所诱导的活动抑制。吗啡对LC诱导的抑制的这种拮抗作用可被纳洛酮逆转或预防，而左啡诺给药可模拟该作用，右啡烷则不能。吗啡增加了浦肯野细胞对平行纤维单突触输入的兴奋性反应，而它通过非阿片受体介导的机制阻断了γ-氨基丁酸诱导的放电抑制。这些结果表明，吗啡干扰了源自LC的突触抑制，并提示这可能是通过激活去甲肾上腺素能神经末梢上的突触前阿片受体而发生的。
