Involvement of neurotransmitters in the action of apelin-13 on passive avoidance learning in mice.

The widespread distribution of apelin-13 and apelin receptors in the brain suggests an important function of this neuropeptide in the brain that has not been explored extensively so far. In the present work, apelin-13 was found to facilitate the consolidation of passive avoidance learning in mice. In order to assess the possible involvement of transmitters in this action, the animals were pretreated with the following receptor blockers in doses which themselves did not influence the behavioral paradigm: phenoxybenzamine (a nonselective α-adrenergic receptor antagonist), propranolol (a β-adrenergic receptor antagonist), cyproheptadine (a nonselective 5-HT2 serotonergic receptor antagonist), atropine (a nonselective muscarinic acetylcholine receptor antagonist), haloperidol (a D2, D3 and D4 dopamine receptor antagonist), bicuculline (a γ-aminobutyric acid subunit A (GABA-A) receptor antagonist), naloxone (a nonselective opioid receptor antagonist), and nitro-L-arginine (a nitric oxide synthase inhibitor). Phenoxybenzamine, cyproheptadine, atropine, haloperidol, bicuculline and nitro-L-arginine prevented the action of apelin-13. Propranolol and naloxone were ineffective. The data suggest that apelin-13 elicits its action on the consolidation of passive avoidance learning via α-adrenergic, 5-HT2 serotonergic, cholinergic, dopaminergic, GABA-A-ergic and nitric oxide mediations.