Behavioral effects of Bj-PRO-7a, a proline-rich oligopeptide from Bothrops jararaca venom

The heptapeptide Bj-PRO-7a, isolated and identified from Bothrops jararaca (Bj) venom, produces antihypertensive and other cardiovascular effects that are independent on angiotensin converting enzyme inhibition, possibly relying on cholinergic muscarinic receptors subtype 1 (M1R). However, whether Bj-PRO-7a acts upon the central nervous system and modifies behavior is yet to be determined. Therefore, the aims of this study were: i) to assess the effects of acute administration of Bj-PRO-7a upon behavior; ii) to reveal mechanisms involved in the effects of Bj-PRO-7a upon locomotion/exploration, anxiety, and depression-like behaviors. For this purpose, adult male Wistar (WT, wild type) and spontaneous hypertensive rats (SHR) received intraperitoneal injections of vehicle (0.9% NaCl), diazepam (2 mg/kg), imipramine (15 mg/kg), Bj-PRO-7a (71, 213 or 426 nmol/kg), pirenzepine (852 nmol/kg), α-methyl-DL-tyrosine (200 mg/kg), or chlorpromazine (2 mg/kg), and underwent elevated plus maze, open field, and forced swimming tests. The heptapeptide promoted anxiolytic and antidepressant-like effects and increased locomotion/exploration. These effects of Bj-PRO-7a seem to be dependent on M1R activation and dopaminergic receptors and rely on catecholaminergic pathways.

从矛头蝮（Bothrops jararaca，简称Bj）毒液中分离鉴定的七肽Bj-PRO-7a，可产生不依赖血管紧张素转换酶抑制的降压及其他心血管效应，其作用机制可能与毒蕈碱型胆碱能受体1亚型（cholinergic muscarinic receptors subtype 1，M1R）有关。然而，目前尚不清楚Bj-PRO-7a是否可作用于中枢神经系统并改变动物行为。因此，本研究的目标为：其一，评估Bj-PRO-7a急性给药对动物行为的影响；其二，阐明Bj-PRO-7a对运动/探索行为、焦虑样行为及抑郁样行为产生影响的潜在机制。为此，成年雄性Wistar野生型（wild type，WT）大鼠与自发性高血压大鼠（spontaneous hypertensive rats，SHR）分别接受腹腔注射赋形剂（0.9%氯化钠溶液）、地西泮（2 mg/kg）、丙咪嗪（15 mg/kg）、Bj-PRO-7a（71、213或426 nmol/kg）、哌仑西平（852 nmol/kg）、α-甲基-DL-酪氨酸（200 mg/kg）或氯丙嗪（2 mg/kg），并依次开展高架十字迷宫、旷场实验与强迫游泳实验。该七肽可诱导产生抗焦虑样与抗抑郁样效应，并增强动物的运动与探索行为。Bj-PRO-7a的上述效应似乎依赖于M1R激活与多巴胺能受体，且通过儿茶酚胺能通路介导。