O'Neill Heidi C, Schmitt Mischel P, Stevens Karen E
Department of Psychiatry, University of Colorado Health Sciences Center, C268-71, 4200 East 9th Avenue, Denver, CO 80262, USA.
Biol Psychiatry. 2003 Oct 15;54(8):847-53. doi: 10.1016/s0006-3223(03)00184-7.
There are similarities between schizophrenia and bipolar disorder, especially during the psychotic phase. Auditory gating deficits are common in both schizophrenia (does not remit postpsychotic event) and bipolar disorder (only during the manic phase). Lithium has been used to treat psychosis acutely in both bipolar disorder and schizophrenia. An animal model was used to assess the effects of lithium treatment on normal and deficient auditory gating.
Mice of the DBA/2 (deficient gating) and C3H (normal gating) strains were treated for 6 weeks with either standard rodent chow or rodent chow supplemented with 2.55g/kg lithium carbonate. After 6 weeks of treatment, auditory evoked potentials were recorded under anesthesia. Differences between the groups and treatments were determined using analysis of variance.
The normally impaired DBA/2 mice showed improved auditory gating following lithium treatment, while the C3H mice, the benchmark "normal" mouse strain, were impaired after lithium treatment.
C3H mice treated with lithium had significantly impaired auditory gating as a result of treatment. This may be due to norepinephrine facilitation, through a blockade of presynaptic alpha(2) autoreceptors. DBA/2 mice had improved gating as a result of treatment with lithium, likely due to improved functioning of the gamma-aminobutyric acid system.
精神分裂症和双相情感障碍之间存在相似之处,尤其是在精神病性发作阶段。听觉门控缺陷在精神分裂症(精神病性发作后不缓解)和双相情感障碍(仅在躁狂发作阶段)中都很常见。锂已被用于急性治疗双相情感障碍和精神分裂症中的精神病症状。使用动物模型来评估锂治疗对正常和缺陷听觉门控的影响。
将DBA/2(门控缺陷)和C3H(正常门控)品系的小鼠用标准啮齿动物饲料或补充有2.55g/kg碳酸锂的啮齿动物饲料治疗6周。治疗6周后,在麻醉下记录听觉诱发电位。使用方差分析确定组间和治疗之间的差异。
正常情况下存在门控缺陷的DBA/2小鼠在锂治疗后听觉门控得到改善,而作为基准“正常”小鼠品系的C3H小鼠在锂治疗后出现门控缺陷。
用锂治疗的C3H小鼠因治疗导致听觉门控显著受损。这可能是由于通过阻断突触前α(2) 自身受体促进去甲肾上腺素释放所致。DBA/2小鼠因锂治疗而门控改善,可能是由于γ-氨基丁酸系统功能改善。