期刊
BEHAVIOURAL PHARMACOLOGY
卷 19, 期 5-6, 页码 548-561出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/FBP.0b013e32830cd822
关键词
antipsychotic drugs; dopamine D(2) receptors; 5-HT(1A) receptors; mouse; prepulse inhibition; schizophrenia; species differences
This study aimed to explore strain and species differences in the involvement of 5-HT(1A) receptors in the action of antipsychotic drugs, using prepulse inhibition (PPI), a model of sensory processing which is deficient in schizophrenia patients. We used automated startle boxes to compare the effect of the 5-HT(1A) receptor agonist, (+/-)-8-hydroxy-dipropyl-amino-tetralin (8-OH-DPAT), on PPI in three mouse strains. Balb/c mice were then pretreated with antipsychotics, treated with 8-OH-DPAT or saline, and tested for PPI. 8-OH-DPAT treatment dose dependently increased PPI in Balb/c mice, but had less effect in 129Sv and C57BI/6 mice. In Balb/c mice, the effect of 8-OH-DPAT was blocked by the typical antipsychotic and dopamine D(2) receptor antagonist, haloperidol and the third generation antipsychotic, aripiprazole, which has activity at both 5-HT(1A) and dopamine D2 receptors. The atypical antipsychotics, clozapine, olanzapine and risperidone, had lesser effects. Similar to our earlier studies in rats, the present PPI results suggest that 5-HT(1A) receptors are involved in the action of some antipsychotic drugs in mice. Despite strain and species differences in the magnitudeand direction of the effect of 8-OH-DPAT, downstream dopamine D(2) receptor activation seems to be an important mediator. These comparative results allow a theoretical framework of receptor interactions, which may guide further studies on the involvement of 5-HT(1A) receptors in schizophrenia.
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