Dept Pharmacobiol CINVESTAV-IPN, México City, 14330, México.
Behav Brain Res. 2013 Sep 1;252:246-51. doi: 10.1016/j.bbr.2013.05.051. Epub 2013 Jun 2.
5-HT5 receptor occurs in brain areas implicated in learning and memory. Hence, the effects (0.01-3.0 mg/kg) of SB-6995516 (a 5-HT5A receptor antagonist) in the associative learning task of autoshaping were studied. The results showed that post-training injection of SB-699551 decreased conditioned responses (CR) during short-term (STM; 1.5h; at 0.1mg/kg) and long-term memory (LTM; 24 h; at 3.0 mg/kg) relative to the vehicle animals. Moreover, considering that there are no selective 5-HT5A receptor agonists, next, diverse doses of the serotonin precursor l-tryptophan were studied during STM and LTM, showing that l-tryptophan (5-100mg/kg) facilitated performance, particularly at 50mg/kg. In interactions experiments, l-tryptophan (50 mg/kg) attenuated the impairment effect induced by SB-699551 (either 0.3 or 3.0 mg/kg). All together this evidence suggests that the blockade of 5-HT5A receptor appear to be able to impair STM and LTM (24 h), while its stimulation might facilitate it. Of course further investigation is necessary, meanly with selective 5-HT5A compounds are necessary.
5-HT5 受体存在于与学习和记忆相关的脑区。因此，研究了 5-HT5A 受体拮抗剂 SB-6995516（0.01-3.0mg/kg）在自动塑形联想学习任务中的作用。结果表明，与载体动物相比，SB-6995516 在短期记忆（STM；1.5h；0.1mg/kg）和长时记忆（LTM；24h；3.0mg/kg）的训练后注射会降低条件反应（CR）。此外，由于没有选择性 5-HT5A 受体激动剂，因此接下来研究了不同剂量的 5-羟色氨酸（血清素前体）在 STM 和 LTM 期间的作用，结果表明 5-羟色氨酸（5-100mg/kg）可改善表现，尤其是在 50mg/kg 时。在相互作用实验中，5-羟色氨酸（50mg/kg）可减弱 SB-699551（0.3 或 3.0mg/kg）引起的损伤作用。所有这些证据表明，5-HT5A 受体的阻断似乎能够损害 STM 和 LTM（24h），而其刺激可能会促进其改善。当然，还需要进一步的研究，特别是使用选择性 5-HT5A 化合物进行研究。
