Weinger M B, Smith N T, Blasco T A, Koob G F
Department of Anesthesiology, University of California, San Diego School of Medicine.
Brain Res. 1991 Mar 29;544(2):181-90. doi: 10.1016/0006-8993(91)90052-w.
Previous work has demonstrated that direct injections of methylnaloxonium (MN), a hydrophilic quaternary opiate antagonist, in the area of the nucleus raphe pontis (RPn) significantly attenuated alfentanil-induced muscle rigidity in the rat. To extend these observations and to explore further the regions important for opiate-induced rigidity, rats were implanted with chronic guide cannulae aimed at discrete brain sites with an emphasis on the region from the periaqueductal grey (PAG) to the RPn. Each animal was pretreated by a blinded observer with an intracerebral injection of MN (125 ng total dose) or saline, and electromyographic (EMG) activity was recorded from the gastrocnemius muscle. Alfentanil (ALF; 500 micrograms/kg) was then administered subcutaneously and the magnitude of tonic EMG activity was assessed as a measure of hindlimb rigidity. The administration of MN into the pontine raphe nucleus (RPn) and also into the more lateral nucleus reticularis tegmenti pontis significantly attenuated ALF rigidity compared with saline-pretreated controls. Within the midbrain, MN selectively reversed rigidity when injected into the periaqueductal grey (PAG). The dorsal PAG appeared to be a more important site than the ventral PAG. There was no significant effect on ALF rigidity of MN injections into brain regions between the ventral PAG and the RPn while MN injections into the deep layers of the superior colliculus, lateral to the dorsal PAG, partially attenuated ALF rigidity. In contrast, rigidity was not consistently reversed after MN injections into the basal ganglia, the dorsal superior colliculus, or the region of the decussation of the dorsal tegmentum. This study provides strong evidence that nuclei of the reticular formation, specifically the PAG, raphe pontis, and reticularis tegmenti pontis that are known to play a role in other opioid-mediated behaviors, are important in opiate-induced muscle rigidity in the rat. These results could have implications for the prevention of this undesirable effect of high-dose opiate administration.
先前的研究表明，在大鼠脑桥中缝核（RPn）区域直接注射亲水性季铵类阿片拮抗剂甲基纳洛酮（MN），可显著减轻阿芬太尼诱导的肌肉强直。为了拓展这些观察结果，并进一步探究对阿片诱导的强直起重要作用的脑区，给大鼠植入了慢性引导套管，目标是离散的脑区，重点是从导水管周围灰质（PAG）到RPn的区域。每只动物由一名不知情的观察者预先经脑内注射MN（总剂量125 ng）或生理盐水进行预处理，然后记录腓肠肌的肌电图（EMG）活动。随后皮下注射阿芬太尼（ALF；500微克/千克），并评估强直EMG活动的幅度，以此作为后肢强直的指标。与生理盐水预处理的对照组相比，向脑桥中缝核（RPn）以及更外侧的脑桥被盖网状核注射MN，可显著减轻ALF诱导的强直。在中脑内，当注射到导水管周围灰质（PAG）时，MN可选择性地逆转强直。背侧PAG似乎比腹侧PAG是更重要的部位。向腹侧PAG和RPn之间的脑区注射MN对ALF诱导的强直没有显著影响，而向背侧PAG外侧的上丘深层注射MN可部分减轻ALF诱导的强直。相比之下，向基底神经节、背侧上丘或背侧被盖交叉区域注射MN后，强直并未持续逆转。这项研究提供了有力证据，表明已知在其他阿片类介导的行为中起作用的网状结构核团，特别是PAG、脑桥中缝核和脑桥被盖网状核，在大鼠阿片诱导的肌肉强直中起重要作用。这些结果可能对预防大剂量阿片类药物给药的这种不良效应具有启示意义。
