The alpha2 adrenoreceptor agonist clonidine suppresses evoked and spontaneous seizures, whereas the alpha2 adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens.
Microinfusion of alpha2 adrenoreceptor agonists and antagonists into amygdala has contrasting effects on evoked and spontaneous seizure susceptibility in amygdala-kindled kittens. Subjects were 14 preadolescent kittens between 3 and 4 months old at the beginning of kindling. The same protocol was followed except that half the kittens received microinfusions (1 mul) of the alpha2 agonist clonidine (CLON; 1.32 nmol), and half received the alpha2 antagonist idazoxan (IDA; 0.33 nmol). Infusions were made over 1 min through needles inserted into cannulae adjacent to stimulating electrodes in the kindled amygdala, and evoked seizures were tested 10-12 min later. The results were: (1) CLON elevated seizure thresholds obtained once at the beginning and end of kindling, but only when compared to sham control values (needle insertion only) in the same animals; IDA significantly reduced thresholds. (2) CLON retarded and IDA accelerated kindling rate, defined as the number of afterdischarges (ADs) required to achieve the first stage 6 seizure or generalized tonic-clonic convulsion (GTC). These effects were most pronounced on the emergence of seizure "generalization" stages (3-6) from "focal" seizure stages (1-2). (3) CLON prevented onset of spontaneous seizures, whereas IDA precipitated onset of spontaneous seizures in 100% of the animals before or during the 5-week post-kindling follow-up during which seizures were evoked once each work day. The study confirms previous findings in kindled rodents to show that CLON and IDA can have opposing effects on kindling development in kittens and is the first report to show contrasting effects on spontaneous epileptogenesis in kindled animals as well.
Shouse
Margaret N
MN
Sleep Disturbance Research (151A3), VA Greater Los Angeles Healthcare System, Sepulveda, CA 91343, USA. nshouse@ucla.edu
Scordato
John C
JC
Farber
Paul R
PR
de Lanerolle
Nihal
N
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000679:Amygdala / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002415:Cats; D003000:Clonidine / Q000494:pharmacology*; D004569:Electroencephalography; D005260:Female; D007839:Functional Laterality; D019329:Idazoxan / Q000494:pharmacology*; D007696:Kindling, Neurologic / Q000187:drug effects*; D008297:Male; D008845:Microinjections; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology; D013238:Stereotaxic Techniques
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D003000:Clonidine; D019329:Idazoxan