Studies on the effects of intrathalamically injected DADL and morphine on nociceptive thresholds and electroencephalographic activity: a thalamic delta receptor syndrome.
Bilateral microinjections of DADL (D-Ala2-D-Leu5-enkephalin) and morphine were carried out in rats in a systematic fashion at histologically identified medial and lateral thalamic sites. DADL produced a dose-dependent (1.5-15.0 nmol), naloxone-reversible (1 mg/kg, i.p.) increase in the hot-plate (HP), tail-flick (TF) and catalepsy (CAT) response latencies with a predominance of activity occurring at lateral as opposed to medial thalamic sites. These effects were seen within 5 min of microinjection. At a significant number of sites, DADL precipitated convulsive seizure activity. Equimolar doses of morphine had a negligible effect on nociceptive indices and were not productive of seizures even at sites where DADL was found to be active. To further examine seizure activity, rats were prepared with bilateral frontal cortical electrodes and microinjected also at medial and lateral thalamic sites with equimolar doses of DADL and morphine (15 nmol). DADL was found to produce electrographically defined seizures unaccompanied by convulsive motor behavior (cataleptic seizures), as well as convulsive seizures. All animals in this group exhibiting analgesia and catalepsy had electrographic evidence of a seizure with markedly abnormal EEG tracings showing postictal spiking and changes in baseline frequency and amplitude. These seizures appeared to be naloxone-reversible. Morphine on the other hand was not productive of seizures, but did produce changes in electroencephalographic activity including spindle bursting, high-voltage slow-frequency activity as well as spiking. As noted, these changes were not associated with any effects on nociceptive measures.
D000818:Animals; D004569:Electroencephalography; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D010146:Pain / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects*; D017465:Receptors, Opioid, delta; D012640:Seizures / Q000139:chemically induced; D012684:Sensory Thresholds / Q000187:drug effects; D013788:Thalamus / Q000187:drug effects*
D011957:Receptors, Opioid; D017465:Receptors, Opioid, delta; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; D009020:Morphine