Hippocampal kindling-induced after-discharge and behavioural depression: immediate and long-term attenuation by opiate antagonists.
Hippocampal kindling results in tonic-clonic convulsions followed by a pronounced period of behavioural depression. The effect of the opiate antagonists, naltrexone and naloxone, on the duration of the after-discharge and behavioural depression was investigated. Naltrexone, injected s.c. 60 min before, significantly reduced the behavioural depression at doses as low as 0.6 mg/kg, but had no effect on the after-discharge even at higher doses. One day later, the behavioural depression was still reduced in some animals and the after-discharge was significantly decreased following the higher doses (0.24-0.48 mg/kg). Naloxone, injected s.c., 10 min before, significantly reduced the behavioural depression at a dose as low as 0.002 mg/kg and also reduced the duration of the after-discharge at some doses. Naloxone did not exert any significant effects 24 h later. Naltrexone, injected i.c. 60 min before kindling in a dose of 1 microgram, significantly attenuated the behavioural depression and had no effect on the after-discharge. The behavioural depression was still attenuated 24 and 48 h later. The involvement of mu-receptor-related endogenous opioid mechanisms in postictal brain processes is suggested. The long-term effects might be related to receptor 'activation' during the immediate period due to an interaction between the antagonist and the kindling experience.
Cottrell
G A
GA
Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
Nyakas
C
C
Bohus
B
B
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D007696:Kindling, Neurologic; D008297:Male; D009271:Naltrexone / Q000008:administration & dosage / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains
D009292:Narcotic Antagonists; D009271:Naltrexone