[D-Pen2, D-Pen5]enkephalin, the standard delta opioid agonist, induces morphine-like behaviors in mice

Area of Science:

• Pharmacology
• Neuroscience
• Opioid Receptor Research

Background:

• Opioid peptides like enkephalins interact with specific receptors in the central nervous system.
• Understanding opioid receptor subtypes (mu, delta) is crucial for developing targeted therapeutics.
• The selective delta opioid receptor agonist [D-Pen2, D-Pen5]enkephalin (DPDPE) has been used to probe delta receptor function.

Purpose of the Study:

• To investigate the receptor mechanisms underlying the behavioral effects of DPDPE.
• To determine the selectivity of DPDPE at different opioid receptor subtypes.
• To compare the effects of DPDPE with a known mu opioid receptor agonist, morphine.

Main Methods:

• Intracerebroventricular (ICV) administration of DPDPE and morphine to ICR mice.
• Observation and quantification of behavioral responses, including Straub tail, locomotion, and circling.
• Pretreatment with opioid receptor antagonists (naloxone, beta-funaltrexamine, ICI 174864) to assess receptor involvement.

Main Results:

• Both DPDPE and morphine induced similar behavioral effects, including Straub tails and increased locomotion.
• DPDPE-induced tail stiffening was attenuated by naloxone and beta-funaltrexamine, suggesting mu receptor involvement.
• ICI 174864, a selective delta opioid receptor antagonist, did not block DPDPE's effects, indicating a loss of delta receptor selectivity at higher doses.

Conclusions:

• Mu opioid receptors mediate the tail stiffening response observed with DPDPE administration.
• Higher doses of DPDPE (10-30 micrograms) result in a loss of selectivity, engaging mu opioid receptors.
• These findings highlight the complex interplay between opioid receptor subtypes and behavioral outcomes.