Delta opioid receptor (DOR) inhibits neurotransmitter release by reducing calcium ion currents and increasing potassium ion conductance. In rats, morphine tolerance is associated with DOR-mediated activation of cortical CCKergic systems. There are indications that some DOR antagonists produce potent antitussive effects and may be considered as candidates of antitussive drugs. In contrast, some DOR agonists have shown antinociceptive, seizuregenic and convulsive properties, implicating a role for the receptor in depression. Clinical experiments have demonstrated that exogenously administered delta opioid peptides had antidepressant activity, suggesting that the receptor may provide a new therapeutic target for treating depression.