ABSTRACT
Influence of neuropeptide kyotorphin (L-thyrosyl-L-arginine) treatment on goldfish Mauthner cells was studied separately or in combination with prolonged natural stimulation of these neurons. The neuroprotective effect of this substance at both functional and ultrastructural levels was demonstrated. Possible mechanisms of kyotorphin action is discussed with regard to its modulating effect on intracellular calcium ion concentration.
Subject(s)
Adaptation, Physiological/drug effects , Analgesics/toxicity , Endorphins/toxicity , Goldfish/physiology , Neurons/ultrastructure , Animals , Endoplasmic Reticulum, Smooth/ultrastructure , Long-Term Potentiation/physiology , Microinjections , Microscopy, Electron , Motor Activity/drug effects , Physical Stimulation , Rotation , Sodium Chloride/pharmacology , Verapamil/pharmacologyABSTRACT
Rats ranging in postnatal age from 6 hours to 28 days were implanted with cortical and depth electrodes as well as an indwelling cannula in the lateral ventricle. We then administered varying amounts of the opiate peptides leucine-enkephalin and beta-endorphin intracerebroventricularly with continuous electroencephalographic monitoring. Leucine-enkephalin produced electrical seizure activity in rats as young as 2 days. beta-Endorphin administration was associated with seizures at the fifth postnatal day, with a high incidence of apnea resulting in death in animals as young as 6 hours. An adult seizure response to beta-endorphin and leucine-enkephalin was seen at 15 and 28 days of age, respectively. Naloxone blocked the seizure produced by these opiate peptides in all age groups. The data indicate that the opiate peptides are potent epileptogenic compounds in developing brain, that seizures induced by leucine-enkephalin differ from those caused by beta-endorphin, and that petit mal-like seizure activity can be an adult response in the rodent.
Subject(s)
Aging , Endorphins/toxicity , Enkephalin, Leucine/toxicity , Seizures/chemically induced , Animals , Brain/drug effects , Electroencephalography , Evoked Potentials/drug effects , Male , Naloxone/pharmacology , Rats , Rats, Inbred Strains , beta-EndorphinABSTRACT
Because endorphin receptor activation alters the function of the central noradrenergic system, opiates may change the regenerative sprouting of neurons in response to adrenergic neurotoxins. To test this hypothesis, newborn rats were treated with several opioids and 6-hydroxydopa (6-OHDOPA) and the development of the noradrenergic system was evaluated. In combination with 6-OHDOPA morphine and naloxone potentiated the development of norepinephrine (NE) levels in the pons-medulla and cerebellum by four weeks of age, beta-Endorphin, Leu- and Met-enkephalin and d-Ala2-enkephalinamide produced a similar effect in the pons-medulla. The effect of morphine was partially attenuated by naloxone. Increased cerebellar noradrenergic histofluorescent staining was observed with the morphine + 6-OHDOPA and naloxone + 6-OHDOPA treatments. Both naloxone and morphine decreased NE levels in the pons-medulla of adult rats treated with 6-OHDOPA. These results suggest that opiates and endorphins may enhance sprouting of noradrenergic neurons following neonatal treatment with 6-OHDOPA, by increasing the toxicity of this neurotoxin.
