Dopamine receptor 3 knockout inhibits acquisition and recall of fear memory induced by electric shocks
10.3867/j.issn.1000-3002.2025.02.001
- VernacularTitle:多巴胺3型受体敲除对电击诱发恐惧记忆形成和唤起的抑制作用
- Author:
Xiaoyan DING
1
;
Zhiyuan WANG
;
Ning WU
;
Jin LI
;
Rui SONG
Author Information
1. 南京中医药大学,江苏 南京 210000;军事医学研究院国家安全特需药品全国重点实验室,神经精神药理学北京市重点实验室,北京 100850
- Publication Type:Journal Article
- Keywords:
dopamine receptor 3;
fear memory;
ventral tegmental area;
dopamine
- From:
Chinese Journal of Pharmacology and Toxicology
2025;39(2):81-88
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE To investigate the effect of dopamine receptor 3(D3R)on fear memory induced by intense electric shocks and the possible neurobiological mechanism.METHODS ① To prevent pain threshold differences from influencing the effect of intense electric shocks,wild-type(WT)and D3R knockout mice(D3R-/-)were used in the Hargreaves test to evaluate their basal pain threshold,with the paw withdrawal latency(PWL)as the observation index.② WT and D3R-/-mice were divided into control groups and model groups,respectively.On the training day(the first day,D 1),the model groups received inescapable electric shocks(1.5 mA,10 s,10 s interval,15 cycle)while the control groups did not.Contextual fear tests were conducted on D2,D7,D10,D14,and D16 after training,with the percentage of freezing time(FT)as the observation index to evaluate fear memory acquisition induced by contextual cues.On D17,after the model groups showed no more fear responses to contex-tual cues,they were re-stimulated with low-intensity current(0.5 mA,10 s,10 s interval,15 cycle)to evoke fear memory.The two control groups did not receive any shocks.Contextual fear tests were conducted on day 18,and the FT%of each group was observed to evaluate fear memory retrieval induced by contextual cues.③ Another cohort of WT and D3R-/-mice was used to further investigate the underlying neural mechanism,with the same grouping and treatment as in ②.Real-time dynamic changes in calcium signals of dopamine(DA)neurons in the ventral tegmental area(VTA)of WT and D3R-/-mice were detected using fiber photometry during electric shocks.The fluorescence area under the curve(AUC)was used as the indicator to quantify the excitability of DA neurons.RESULTS ① In the Hargreaves test,there was no significant difference in PWL between D3R-/-mice and WT mice,indi-cating the two genotype mice had no significant differences in the basal pain threshold.② Compared with the WT control group,the percentage of FT of the WT model group significantly increased on D2,D7,D10,and D14(P<0.05).Compared with the D3R-/-control group,the percentage of FT of the D3R-/-model group significantly increased only on D2 and D7(P<0.01).Meanwhile,the percentage of the FT of D3R-/-model group was significantly lower than in the WT control group on D2,D7,D10,and D14(P<0.05,P<0.01).During memory recall(D18),the percentage of FT of the WT model and D3R-/-model groups significantly increased compared to their respective control groups(P<0.01,P<0.05),while the percentage of FT of D3R-/-model mice was significantly lower than that of WT model mice(P<0.01).③ In the fiber photometry test,during the shock period,the calcium signals of DA neurons in the VTA of WT model and D3R-/-model mice rapidly increased within the first 2 s,and then gradually decreased between 2 to 10 s.The AUC within the 2 to 10 s interval was significantly lower in D3R-/-model mice compared to WT model mice(P<0.05),indicating that the excitability of DA neurons in the VTA of D3R-/-model mice was significantly lower than that of WT-model mice.CONCLUSION D3R knockout inhibits the acquisition and recall of long-term fear memory in mice,and its neurobiological mechanism may be related to the decreased excitability of DA neurons during electric shock.
