Blockade of 5-HT2a receptors reduces haloperidol-induced attenuation of reward
Blockade of 5-HT2a receptors reduces haloperidol-induced attenuation of reward
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DOI：
10.1038/sj.npp.1301136
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发表时间：
2007-03-01
影响因子：
7.6
通讯作者：
Rompre, Pierre-Paul
中科院分区：
文献类型：
--
作者：
Benaliouad, Faiza;Kapur, Shitij;Rompre, Pierre-Paul
Previous studies have shown that effective antipsychotic medications attenuate reward, an effect that is generally attributed to their effectiveness at blocking the dopamine D2- like receptors. As blockade of the serotonin type 2a ( 5- HT2a) receptors is a common property of the newer antipsychotics, the present study compared the effect of haloperidol, clozapine, and M100907 ( a selective 5- HT2a antagonist) and the combined effect of haloperidol and M100907 treatment on brain stimulation reward ( BSR). Experiments were performed on male Sprague - Dawley rats trained to produce an operant response to obtain electrical stimulation in the lateral hypothalamus. Measures of reward threshold were determined in different groups of rats using the curve- shift method using fixed current intensity and variable frequency before and at different times after injection of haloperidol ( 0.01, 0.05, 0.1, and 0.25 mg/ kg), clozapine ( 1, 7.5, 15, and 30 mg/ kg), M100907 ( 0.033, 0.1, and 0.3 mg/ kg), or their vehicle. The effect of M100907 ( 0.3 mg/ kg) on the attenuation of BSR by a sub- and suprathreshold dose of haloperidol was studied in another group of rats. Clozapine produced a dose- orderly increase in reward threshold with a mean maximal increase of 50%; at high doses, clozapine induced cessation of responding in several animals at different time periods. Haloperidol induced a dose- dependent increase in reward threshold, with the mean maximal increase ( 75%) being observed at the highest dose; it also produced a dose- dependent reduction of maximum rates of responding. M100907 failed to alter reward at any of the doses tested and had no effect on the subthreshold dose ( 0.01 mg/ kg) of haloperidol. But when combined with a suprathreshold dose of haloperidol, M100907 reduced the reward- attenuating effect of haloperidol. These results show that 5- HT2a receptors are unlikely to constitute a component of the reward- relevant pathway activated by lateral hypothalamic stimulation. However, blockade of 5- HT2a receptors may account for the relatively lower level of reward attenuation produced by clozapine, and predict that antipsychotic medications that have a high affinity for the 5- HT2a receptor may be less likely to induce dysphoria.
