LAUSR

HighlightsLVV‐h6 increased the number of entries and the time spent in open arms of the maze, an indicative of anxiolysis.LVV‐h6 provoked antidepressant effect in the forced swimming test.LVV‐h6 increased the exploration.LVV‐h6 did not change the cardiovascular and neuroendocrine reactivities to acute stress. ABSTRACT LVV‐hemorphin‐6 (LVV‐h6) is bioactive peptide and is a product of the degradation of hemoglobin. Since LVV‐h6 effects are possibly mediated by opioid or AT4/IRAP receptors, we hypothesized that LVV‐h6 would modify behavior. We evaluated whether LVV‐h6 affects: i) anxiety‐like behavior and locomotion; ii) depression‐like behavior; iii) cardiovascular and neuroendocrine reactivity to emotional stress. Male Wistar rats (± 300 g) received LVV‐h6 (153 nmol/kg i.p.) or vehicle (NaCl 0.9% i.p.). We used: i) open field (OF) test for locomotion; ii) elevated plus maze (EPM) for anxiety‐like behavior; iii) forced swimming test (FST) for depression‐like behavior and iv) air jet for cardiovascular and neuroendocrine reactivity to stress. Diazepam (2 mg/kg i.p.) and imipramine (15 mg/kg i.p.) were used as positive control for EPM and FST, respectively. To evaluate the LVV‐h6 mechanisms, we used: the antagonist of oxytocin (OT) receptors (atosiban – ATS 1 and 0.1 mg/kg i.p.); the inhibitor of tyrosine hydroxylase (Alpha‐methyl‐p‐tyrosine – AMPT 200 mg/kg i.p.) to investigate the involvement of catecholaminergic paths; and the antagonist of opioid receptors (naltrexone – NTX 0.3 mg/kg s.c.). We found that LVV‐h6: i) evoked anxiolytic‐like effect; ii) evoked antidepressant‐like effect in the FST; and iii) did not change the locomotion, neuroendocrine and cardiovascular responses to stress. The LVV‐h6 anxiolytic‐like effect was not reverted by ATS and AMPT. However, the antidepressant effects were reverted only by NTX. Hence, our findings demonstrate that LVV‐h6 modulates anxiety‐like behavior by routes that are not oxytocinergic, catecholaminergic or opioid. The antidepressant‐like effects of LVV‐h6 rely on opioid pathways.