Tamminga C A, Dale J M, Goodman L, Kaneda H, Kaneda N
Department of Psychiatry, University of Maryland, Baltimore 21228.
Psychopharmacology (Berl). 1990;102(4):474-8. doi: 10.1007/BF02247127.
Vacuous chewing movements (VCMs) in three different rat strains developed at considerably different rates after 19 weeks of continual haloperidol treatment at an average daily dose of 1.5 mg/kg. Sprague Dawley (SD) rats displayed relatively high rates of VCMs with low variability, compared to Wistar (W) and Long Evan (LE) rats. Atropine decreased but did not abolish VCMs in two of the three strains (LE greater than SD). After haloperidol withdrawal, VCMs remitted gradually in all strains, but least rapidly in the SD rats. In a separate group of SD rats. VCMs were rated weekly from the start of haloperidol treatment and showed considerable interindividual variability. Even after 24 weeks of continuous haloperidol, 12 out of 32 treated rats showed no VCMs at all, while 13 out of 32 had intense movements, analogous to the clinical situation in which only some patients treated with neuroleptics develop tardive dyskinesia. These results indicate that there are individual and strain differences in the development of VCMs, and suggest that there may also be genetically determined differences in the development of tardive dyskinesia.
在以平均每日剂量1.5毫克/千克持续给予氟哌啶醇治疗19周后,三种不同品系的大鼠出现的空嚼运动(VCMs)发展速度差异显著。与Wistar(W)大鼠和Long Evan(LE)大鼠相比,Sprague Dawley(SD)大鼠表现出相对较高的VCMs发生率且变异性较低。阿托品可降低但不能消除三种品系中两种的VCMs(LE大鼠大于SD大鼠)。停用氟哌啶醇后,所有品系的VCMs均逐渐缓解,但SD大鼠缓解速度最慢。在另一组SD大鼠中,从开始给予氟哌啶醇治疗起每周对VCMs进行评分,结果显示个体间存在显著差异。即使在持续给予氟哌啶醇24周后,32只接受治疗的大鼠中有12只根本没有出现VCMs,而32只中有13只出现剧烈运动,这类似于临床情况,即只有一些接受抗精神病药物治疗的患者会发生迟发性运动障碍。这些结果表明,VCMs的发展存在个体和品系差异,并提示迟发性运动障碍的发展可能也存在基因决定的差异。