Circuit specific functions of cannabinoid CB1 receptor in the balance of investigatory drive and exploration.
Circuit specific functions of cannabinoid CB1 receptor in the balance of investigatory drive and exploration.
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DOI：
10.1371/journal.pone.0026617
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Lutz B
中科院分区：
文献类型：
--
作者：
Häring M;Kaiser N;Monory K;Lutz B
平衡的新奇寻求和探索是生存的基本行为，并被发现在几种精神障碍中功能失调。最近的研究表明，内源性大麻素(ECB)系统是研究驱动力的重要控制系统。用大麻能药物对啮齿动物进行药物治疗会导致社会和对象调查的改变。有趣的是，根据治疗、药物浓度和实验条件的不同，得到了相互矛盾的结果。大麻素1型受体(CB1)是ECB系统的中枢成分，主要分布在两个相对的神经元群体的突触上，即抑制性GABA能神经元和兴奋性谷氨酸能神经元。在本研究中，我们使用不同的转基因小鼠品系，旨在研究谷氨酸或GABA能神经元中CB1受体失活对研究行为的影响。我们在三种不同的范式中评估了有生命的(互动伙伴)和无生命的(物体)探索行为。我们发现，当皮质和纹状体GABA能神经元中的CB1受体被删除时，探索就会增加。当CB1受体特异性地从表达多巴胺受体D1的纹状体GABA能培养的刺神经元中删除时，没有观察到任何影响。相反，皮质谷氨酸能神经元中CB1受体的缺失导致探查减少。因此，我们的结果表明，通过激活皮质谷氨酸和GABA能神经元上的CB1受体，欧洲央行系统在社会和非社会背景下都准确地平衡了探索行为。此外，这些结果可以解释以前药理学研究的相互矛盾的发现，并可能进一步表明，有可能重新调整在精神障碍中观察到的探索行为的不平衡。
Well balanced novelty seeking and exploration are fundamental behaviours for survival and are found to be dysfunctional in several psychiatric disorders. Recent studies suggest that the endocannabinoid (eCB) system is an important control system for investigatory drive. Pharmacological treatment of rodents with cannabinergic drugs results in altered social and object investigation. Interestingly, contradictory results have been obtained, depending on the treatment, drug concentration and experimental conditions. The cannabinoid type 1 (CB1) receptor, a central component of the eCB system, is predominantly found at the synapses of two opposing neuronal populations, i.e. on inhibitory GABAergic and excitatory glutamatergic neurons. In the present study, using different transgenic mouse lines, we aimed at investigating the impact of CB1 receptor inactivation in glutamatergic or GABAergic neurons on investigatory behaviour. We evaluated animate (interaction partner) and inanimate (object) exploratory behaviour in three different paradigms. We show that exploration was increased when CB1 receptor was deleted from cortical and striatal GABAergic neurons. No effect was observed when CB1 receptor was deleted specifically from dopamine receptor D1-expressing striatal GABAergic medium spiny neurons. In contrast, deletion of CB1 receptor from cortical glutamatergic neurons resulted in a decreased exploration. Thus, our results indicate that exploratory behaviour is accurately balanced in both, the social and non-social context, by the eCB system via CB1 receptor activation on cortical glutamatergic and GABAergic neurons. In addition, the results could explain the contradictory findings of previous pharmacological studies and could further suggest a possibility to readjust an imbalance in exploratory behaviour observed in psychiatric disorders.
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DOI：
10.1177/0269881111408958
发表时间：
2012-01
期刊：
Journal of psychopharmacology (Oxford, England)
影响因子：
--
作者：
Ruehle S;Rey AA;Remmers F;Lutz B
通讯作者：
Lutz B
影响因子：
2.7
作者：
ENNACEUR, A;DELACOUR, J
通讯作者：
DELACOUR, J
影响因子：
5.3
作者：
Katona, István;Urbán, Gabriella M.;Freund, Tamás F.
通讯作者：
Freund, Tamás F.
影响因子：
3.4
作者：
Martin, M;Ledent, C;Valverde, O
通讯作者：
Valverde, O
影响因子：
16.2
作者：
Monory, Krisztina;Massa, Federico;Lutz, Beat
通讯作者：
Lutz, Beat