Knockout and pharmacological studies have shown that delta opioid peptide (DOP) receptor
signalling regulates emotional responses. In the present study, the in vitro and in vivo
pharmacological profile of the DOP ligand, H-Dmt-Tic-NH-CH(CH2-COOH)-Bid (UFP-512) was
investigated. In receptor binding experiments performed on membranes of CHO cells
expressing the human recombinant opioid receptors, UFP-512 displayed very high affinity
(pKi 10.20) and selectivity (>150-fold) for DOP sites. In functional studies ([35S]GTPgS binding
in CHOhDOP membranes and electrically stimulated mouse vas deferens) UFP-512 behaved
as a DOP selective full agonist showing potency values more than 100-fold higher than
DPDPE. In vivo, in the mouse forced swimming test, UFP-512 reduced immobility time both
after intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administration. Similar effects
were recorded in rats. Moreover, UFP-512 evoked anxiolytic-like effects in the mouse
elevated plus maze and light-dark aversion assays. All these in vivo actions of UFP-512
were fully prevented by the selective DOP antagonist naltrindole (3 mg/kg, s.c.). In conclusion,
the present findings demonstrate that UFP-512 behaves as a highly potent and selective
agonist at DOP receptors and corroborate the proposal that the selective activation of DOP
receptors elicits robust anxiolytic- and antidepressant-like effects in rodents