Kaster Manuella P, Budni Josiane, Santos Adair R S, Rodrigues Ana Lúcia S
Departamento de Bioquímica, Centro de Ciências Biológicas, Universidade Federal de Santa Catarina, Campus Universitário - Trindade-88040-900, Florianópolis-SC, Brazil.
Eur J Pharmacol. 2007 Dec 8;576(1-3):91-8. doi: 10.1016/j.ejphar.2007.08.026. Epub 2007 Aug 25.
This study investigated the involvement of the opioid system in the antidepressant-like effect of adenosine in the forced swimming test. The effect of adenosine (10 mg/kg, i.p.) was prevented by the pretreatment of mice with naloxone (1 mg/kg, i.p., a nonselective opioid receptor antagonist), naltrindole (3 mg/kg, i.p., a selective delta-opioid receptor antagonist), clocinnamox (1 mg/kg, i.p., an irreversible mu-opioid receptor antagonist), and 2-(3,4-dichlorophenyl)-Nmethyl-N-[(1S)-1-(3-isothiocyanatophenyl)-2-(1-pyrrolidinyl)ethyl]acetamide (DIPPA; 1 mg/kg, i.p., a selective kappa-opioid receptor antagonist), but not with naloxone methiodide (1 mg/kg, s.c., a nonselective opioid receptor antagonist that does not cross the blood-brain barrier). Naloxone also prevented the anti-immobility effect of cyclohexyladenosine (CHA, 0.1 mg/kg, i.p., a selective adenosine A(1) receptor agonist) and N6-[2-(3,5-dimethoxyphenyl)-2-(2-methylphenyl)ethyl]adenosine (DPMA, 1 mg/kg, i.p., a selective adenosine A(2A) receptor agonist). The administration of DIPPA (0.1 mg/kg, i.p.) or morphine (1 mg/kg, s.c., a nonselective opioid receptor agonist), but not naltrindole (0.3 mg/kg, i.p.) and clocinnamox (0.1 mg/kg, i.p.) potentiated the effect of a subeffective dose of adenosine (1 mg/kg, i.p.) in the forced swimming test, without affecting the locomotor activity. No additive effect in the immobility time was observed when mice were treated with morphine (5 mg/kg, s.c.) plus adenosine (10 mg/kg, i.p.). These results indicate that the anti-immobility effect of adenosine in the forced swimming test, via adenosine A(1) and A(2A) receptors, is mediated by an interaction with the opioid system, likely dependent on an activation of mu- and delta-opioid receptors and an inhibition of kappa-opioid receptors.
本研究在强迫游泳试验中调查了阿片系统在腺苷抗抑郁样效应中的作用。用纳洛酮（1mg/kg，腹腔注射，一种非选择性阿片受体拮抗剂）、纳曲吲哚（3mg/kg，腹腔注射，一种选择性δ-阿片受体拮抗剂）、氯辛肟（1mg/kg，腹腔注射，一种不可逆的μ-阿片受体拮抗剂）和2-（3,4-二氯苯基）-N-甲基-N-[(1S)-1-(3-异硫氰酸苯酯)-2-(1-吡咯烷基)乙基]乙酰胺（DIPPA；1mg/kg，腹腔注射，一种选择性κ-阿片受体拮抗剂）预处理小鼠可阻断腺苷（10mg/kg，腹腔注射）的作用，但用甲硫氨酸纳洛酮（1mg/kg，皮下注射，一种不穿过血脑屏障的非选择性阿片受体拮抗剂）预处理则不能。纳洛酮还可阻断环己基腺苷（CHA，0.1mg/kg，腹腔注射，一种选择性腺苷A(1)受体激动剂）和N6-[2-(3,5-二甲氧基苯基)-2-(2-甲基苯基)乙基]腺苷（DPMA，1mg/kg，腹腔注射，一种选择性腺苷A(2A)受体激动剂）的抗不动效应。在强迫游泳试验中，给予DIPPA（0.1mg/kg，腹腔注射）或吗啡（1mg/kg，皮下注射，一种非选择性阿片受体激动剂）可增强亚有效剂量腺苷（1mg/kg，腹腔注射）的效应，但给予纳曲吲哚（0.3mg/kg，腹腔注射）和氯辛肟（0.1mg/kg，腹腔注射）则不能，且不影响运动活性。当小鼠用吗啡（5mg/kg，皮下注射）加腺苷（10mg/kg，腹腔注射）处理时，未观察到不动时间上的相加效应。这些结果表明，在强迫游泳试验中，腺苷通过腺苷A(1)和A(2A)受体产生的抗不动效应是通过与阿片系统相互作用介导的，可能依赖于μ-和δ-阿片受体的激活以及κ-阿片受体的抑制。
