TY - JOUR
T1 - Systemic morphine blocks the seizures induced by intracerebroventricular (i.c.v.) injections of opiates and opioid peptides
AU - Urca, Gideon
AU - Frenk, Hanan
N1 - Funding Information:
This work was supported by a grant of the Israel National Council for Research and Development to H.F., and by a grant from the Israel National Academy of Sciences to G.U. The naloxone used was a gift from Endo Laboratories, Garden City, N.Y.
PY - 1982/8/19
Y1 - 1982/8/19
N2 - Intracerebroventricular (i.c.v.) injections of the endorphins and of morphine in rats produce highly characteristic, naloxone sensitive, electrographic seizures. In contrast, systemic injections of morphine have been shown to exert a marked anticonvulsant effect. The present study demonstrates that systemic morphine pretreatment can prevent the occurrence of electrographic seizures induced by i.c.v. morphine, Leu-enkephalin and β-endorphin and that the anti-epileptic effect of morphine can be reversed by naloxone. Male albino rats, previously prepared for chronic i.c.v. injections and EEG recording, were pretreated with 0-100 mg/kg of intraperitoneal (i.p.) morphine. Thirty five minutes later morphine (520 nmol), Leu-enkephalin (80 nmol) or β-endorphin (5 nmol) were injected i.c.v. Pretreatment with i.p. morphine blocked the occurrence of seizures induced by morphine and both endogenous opioids. Lower doses of systemic morphine (50 mg/kg) were necessary to block i.c.v. morphine seizures than the dose (100 mg/kg) necessary to block seizures induced by i.c.v. Leu-enkephalin and β-endorphin. Naloxone (1 mg/kg) administered 25 min following 50 mg/kg of i.p. morphine and preceding the injections of i.c.v. morphine reversed the antiepileptic effect of systemic morphine. These results demonstrate the possible existence of two opiate sensitive systems, one with excitatory-epileptogenic effects and the other possessing inhibitory-antiepileptic properties. The possible relationship between these findings and the known heterogeneity of opiate receptors and opiate actions is discussed.
AB - Intracerebroventricular (i.c.v.) injections of the endorphins and of morphine in rats produce highly characteristic, naloxone sensitive, electrographic seizures. In contrast, systemic injections of morphine have been shown to exert a marked anticonvulsant effect. The present study demonstrates that systemic morphine pretreatment can prevent the occurrence of electrographic seizures induced by i.c.v. morphine, Leu-enkephalin and β-endorphin and that the anti-epileptic effect of morphine can be reversed by naloxone. Male albino rats, previously prepared for chronic i.c.v. injections and EEG recording, were pretreated with 0-100 mg/kg of intraperitoneal (i.p.) morphine. Thirty five minutes later morphine (520 nmol), Leu-enkephalin (80 nmol) or β-endorphin (5 nmol) were injected i.c.v. Pretreatment with i.p. morphine blocked the occurrence of seizures induced by morphine and both endogenous opioids. Lower doses of systemic morphine (50 mg/kg) were necessary to block i.c.v. morphine seizures than the dose (100 mg/kg) necessary to block seizures induced by i.c.v. Leu-enkephalin and β-endorphin. Naloxone (1 mg/kg) administered 25 min following 50 mg/kg of i.p. morphine and preceding the injections of i.c.v. morphine reversed the antiepileptic effect of systemic morphine. These results demonstrate the possible existence of two opiate sensitive systems, one with excitatory-epileptogenic effects and the other possessing inhibitory-antiepileptic properties. The possible relationship between these findings and the known heterogeneity of opiate receptors and opiate actions is discussed.
KW - anticonvulsant action
KW - convulsant action
KW - endogenous opioids
KW - naloxone
KW - opiates
UR - http://www.scopus.com/inward/record.url?scp=0019960927&partnerID=8YFLogxK
U2 - 10.1016/0006-8993(82)90148-2
DO - 10.1016/0006-8993(82)90148-2
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0019960927
VL - 246
SP - 121
EP - 126
JO - Brain Research
JF - Brain Research
SN - 0006-8993
IS - 1
ER -