GABAergic influences on plus-maze behaviour in mice
GABAergic influences on plus-maze behaviour in mice
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DOI：
10.1007/s002130050148
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发表时间：
1996-12-01
影响因子：
3.4
通讯作者：
Rodgers, RJ
中科院分区：
文献类型：
--
作者：
Dalvi, A;Rodgers, RJ
已发现GABA功能的操纵在焦虑的动物模型中产生高度可变的影响。在本系列中，行为学版本的小鼠高架十字迷宫被用来详细检查地西泮的行为概况（1.5 mg/kg;阳性对照）和一系列GABA相关化合物：丙戊酸（100-400 mg/kg），No-711（1.25-10.0 mg/kg），蝇蕈醇0 mg/kg）、（+）荷包牡丹碱（4.0-8.0 mg/kg）、印防己毒素（0.25-2.0 mg/kg）、R（+）巴氯芬（0.375-3.0 mg/kg）和CGP 35348（25-200 mg/kg）。在常规和行为学指标上，结果证实了地西泮在当前试验条件下的抗焦虑作用，并显示了GABA-T抑制剂丙戊酸（100-400 mg/kg）和GABA（A）受体激动剂蝇蕈醇（2 mg/kg）的基本相似作用。GABA再摄取抑制剂No-711在低剂量（1.25-2.5 mg/kg）下产生弱的抗焦虑样作用，但在最高试验剂量（10 mg/kg）下破坏行为。虽然GABA（A）受体拮抗剂（+）荷包牡丹碱和印防己毒素产生了焦虑增强的变化，但在高剂量（分别为8 mg/kg和1-2 mg/kg）下，伴随的行为抑制是明显的。进一步的研究表明，观察到的荷包牡丹碱的作用可能是由活性代谢物介导的，如荷包牡丹碱。与丙戊酸和直接GABA（A）受体操作的作用相反，GABA（B）受体激动剂R（+）巴氯芬在最高试验剂量（3 mg/kg）下非特异性破坏行为，而GABA（B）受体拮抗剂CGP 35348在研究的剂量范围内无活性。尽管目前的数据证实了十字迷宫对修饰GABA（A）受体功能的药物的敏感性，但为了更充分地表征这种关系，还需要进一步的研究。
Manipulations of GABA function have been found to produce highly variable effects in animal models of anxiety. In the present series, an ethological version of the murine elevated plus-maze was used to examine in detail the behavioural profiles of diazepam (1.5 mg/kg; positive control) and a range of GABA-related compounds: valproic acid (100-400 mg/kg), No-711 (1.25-10.0 mg/kg), muscimol (0.5-3.0 mg/kg), (+)bicuculline (4.0-8.0 mg/kg), picrotoxin (0.25-2.0 mg/kg), R(+)baclofen (0.375-3.0 mg/kg) and CGP 35348 (25-200 mg/kg). On both conventional and ethological indices, results confirmed the anxiolytic profile of diazepam under present test conditions, and revealed substantially similar effects for the GABA-T inhibitor, valproic acid (100-400 mg/kg), and the GABA(A) receptor agonist, muscimol (2 mg/kg). The GABA reuptake inhibitor, No-711, produced weak anxiolytic-like effects at low doses (1.25-2.5 mg/kg) but disrupted behaviour at the highest dose tested (10 mg/kg). Although the GABA(A) receptor antagonists, (+)bicuculline and picrotoxin, produced changes indicative of anxiety enhancement, concomitant behavioural suppression was evident at high doses (8 mg/kg and 1-2 mg/kg, respectively). Further studies suggested that the effects observed with bicuculline may be mediated by an active metabolite, such as bicucine. In contrast to the effects of valproic acid and direct GABA(A) receptor manipulations, the GABA(B) receptor agonist, R(+) baclofen, non-specifically disrupted behaviour at the highest dose tested (3 mg/kg) while the GABA(B) receptor antagonist, CGP 35348, was inactive over the dose range studied. Although present data confirm the sensitivity of the plus-maze to agents which modify GABA(A) receptor function, further studies will be required in order more fully to characterize this relationship.