Effects of 2-bromoterguride, a dopamine D2 receptor partial agonist, on cognitive dysfunction and social aversion in rats

多巴胺 D2 受体部分激动剂 2-溴特罗脲对大鼠认知功能障碍和社会厌恶的影响

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作者:Emilia Tarland, Robert T Franke, Heidrun Fink, Heinz H Pertz, Jan Brosda

Conclusions

Our data support 2-bromoterguride as a promising APD candidate due to its beneficial effect on cognitive impairments and negative symptoms of schizophrenia.

Objective

In continuation of our recent work, we now investigated the effect of 2-bromoterguride on apomorphine and phencyclidine (PCP)-induced disruptions of prepulse inhibition (PPI) of the acoustic startle response, a measure of sensory gating. In addition, we used subchronic PCP treatment to produce cognitive deficits and social aversion, and assessed the effect of 2-bromoterguride on the performance in the novel object recognition (NOR) task (model for studying cognitive deficit symptoms of schizophrenia) and the social interaction test (model for studying negative symptoms of schizophrenia). Finally, we extended the side effect profile of 2-bromoterguride by measuring the prolactin response to systemic administration of the drug in rats.

Results

Treatment with 2-bromoterguride (0.1 and 0.3 mg/kg) reversed PPI deficits induced by apomorphine and PCP, respectively. Subchronic PCP induced impairments in object memory and social interaction behavior which were ameliorated by 2-bromoterguride but not by clozapine and aripiprazole, respectively. Prolactin concentration in blood serum was not elevated at 1, 2, or 4 h post-2-bromoterguride treatment, which further supports the safe and effective use of this drug. Conclusions: Our data support 2-bromoterguride as a promising APD candidate due to its beneficial effect on cognitive impairments and negative symptoms of schizophrenia.

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