安定对大鼠开场行为活动和高钾诱发单胺递质释放的影响

急性ip安定3mg/kg显著抑制大鼠开场(OF)行为活动。慢性ip同一剂量安定15d,对OF抑制产生耐受。完成OF观察后,断头取脑,观察高K⁺诱发不同脑区单胺递质释放变化。整体急性ip安定3mg/kg产生与离体条件下9μmol/L安定相似的抑制高K⁺诱发单胺递质释放作用。慢性ip安定,对海马和杏仁核区高K~+诱发儿茶酚胺释放抑制作用产生显著耐受;未观察到对高K⁺诱发5-羟色胺抑制作用的耐受现象。

EFFECTS OF DIAZEPAM ON THE RAT OPEN FIELD BEHAVIOR AND HIGH K+ INDUCED RELEASE OF MONOAMINE NEUROTRANSMITTERS FROM BRAIN SLICES

Acute i. p injection of diazepam (3 mg/kg) significantly decreased the open field behaviors (locomotion and rearing) of rats. However, when diazepam (3 mg/kg) was given ip daily for 15 consecutive days, no depressive effect on the open field behaviors was observed. After the open field observation, rats were immediately decapitated and brain slices of cortex, hippocampus, amygdala and brain stem were stimulated by high K+ (65 mmol/L) to cause the release of noradrenaline (NA), dopamine (DA) and serotonin (5-HT). Diazepam (9 mumol/Ls) significantly depressed the release of monoamine neurotransmitters caused by high K+, which were antagonized by Ro 15-1788 (5 mumol/L) in vitro. Acute administration of diazepam (ip 3 mg/kg) also significantly depressed the release of monoamine neurotransmitters caused by high K+ from all regions observed. However, hippocampus showed tolerance to the depressive effects of diazepam on the releases of NA and DA, and amygdala only on the release of DA, caused by high K+, when given ip chronically (3 mg/kg, 15 d). Our results suggest that the depressive effect of benzodiazepines on the release caused by anxiogenic factors of catecholamine in the hippocampus, front cortex and amygdala regions may be one of the mechanisms of sedative and anxiolytic actions of benzodiazepines.