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Delta opiate receptors are involved in the endopioid-induced myoclonic contractions
Abstract:
Morphine, the prototype mu opiate receptor agonist, decreased the spontaneous and [D-Ala2]-Met-enkephalinamide (DALA)-induced myoclonic contractions (MC) of submandibular muscles in the anaesthetized rat. The proposed kappa receptor agonists ketocyclazocine, ethylketocyclazocine and bremazocine failed to induce MC. In addition, bremazocine inhibited the spontaneous and DALA induced MC. Cyclazocine, the so-called sigma opiate receptor agonist, had a weak potency in generation of MC, but without step dose response tendency. The most potent opioid peptide in inducing the MC and electrocortical (ECoG) epileptic pattern was the delta opiate receptor agonist [D-Ala2,D-Leu5]-enkephalin (DADL). All drugs were administered intraventricularly. The results indicate that myoclonic phenomena induced by DADL and probably by other endopioids are mediated by delta opiate receptors in the rat brain. It is suggested that the combined ECoG and EMG method used in this study offers an opportunity to define further the biological role of opiate receptors and to identify the potential delta opiate receptor acting drugs, which might provide a new approach to the therapy of some seizure disorders.
Insights
Delta opiate receptor agonists, like DADL, induce myoclonic contractions (MC) in rats. This study suggests delta opiate receptors mediate these effects, offering potential for new seizure disorder therapies.
Area of Science:
- Neuroscience
- Pharmacology
- Opiate Receptor Research
Background:
- Morphine, a mu opiate agonist, reduced muscle contractions.
- Kappa and sigma opiate receptor agonists showed limited effects on myoclonic contractions (MC).
Purpose of the Study:
- To investigate the role of different opiate receptor subtypes in inducing myoclonic contractions (MC) and electrocortical (ECoG) epileptic patterns.
- To identify the most potent opioid peptide for inducing MC and ECoG epileptic patterns.
Main Methods:
- Intraventricular administration of various opiate receptor agonists and antagonists in anesthetized rats.
- Simultaneous recording of myoclonic contractions (MC) using electromyography (EMG) and electrocortical (ECoG) activity.
Main Results:
- The delta opiate receptor agonist [D-Ala2,D-Leu5]-enkephalin (DADL) was the most potent inducer of MC and ECoG epileptic patterns.
- Morphine decreased spontaneous and DALA-induced MC, while bremazocine inhibited them.
- Cyclazocine showed weak, inconsistent MC generation.
Conclusions:
- Myoclonic phenomena induced by DADL and other endopioids are mediated by delta opiate receptors in the rat brain.
- The combined ECoG and EMG method is valuable for understanding opiate receptor functions.
- Identifying delta opiate receptor agonists may lead to novel therapies for seizure disorders.