The effect of CA1 dopaminergic system on amnesia induced by harmane in mice.

Abstract

In the present study, the effects of bilateral injections of dopaminergic drugs into the hippocampal CA1 regions (intra-CA1) on harmane-induced amnesia were examined in mice. We used a single-trial step-down inhibitory avoidance task for the assessment of memory acquisition in adult male mice. Our data indicated that pre-training intra-peritoneal (i.p.) administration of harmane (12mg/kg) impaired memory acquisition. Moreover, intra-CA1 administration of dopamine D1 receptor agonist, SKF38393 (0.25µg/mouse), dopamine D1 receptor antagonist, SCH23390 (0.25µg/mouse), dopamine D2 receptor agonist, quinpirole (0.125 and 0.25µg/mouse) and dopamine D2 receptor antagonist, sulpiride (0.2 and 0.4µg/mouse) decreased the learning of a single-trial inhibitory avoidance task. Furthermore, pre-training intra-CA1 injection of sub-threshold doses of SKF38393 (0.0625µg/mouse) or sulpiride (0.1µg/mouse) increased pre-training harmane (4 and 8mg/kg, i.p.)-induced amnesia. On the other hand, pre-training intra-CA1 injection of a sub-threshold dose of SCH23390 (0.0625µg/mouse) reversed amnesia induced by an effective dose of harmane (12mg/kg; i.p.). In addition, Pre-training intra-CA1 injection of quinpirole (0.0625µg/mouse) had no effect on memory impairment induced by harmane. These findings indicate the involvement of CA1 dopaminergic system on harmane-induced impairment of memory acquisition.