Abstracts

Rationale: Microinfusion of α2 adrenoreceptor agonists and antagonists into amygdala have contrasting effects on evoked and spontaneous seizure susceptibility in amygdala-kindled kittens. Methods: Subjects were 14 preadolescent kittens between 3-4 months old at the beginning of kindling. The same protocol of interspersed experimental and control procedures was followed except that half the kittens received microinfusions (1µL) of the α2 agonist clonidine (CLON; 1.32 nmol), and half received the α2 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. Evoked seizure variables (threshold, duration, seizure stage, kindling rate) were tested 10-12 minutes after electrically induced afterdischarge (AD)as specified in the Results. Spontaneous seizures, defined as a seizure documented on periodic split-screen EEG-behavioral video or 24h behavioral video recordings in the vivarium, were also assessed throughout. Results: Statistically significant results (p< .05) were based upon one or two-way analysis of variance with post hoc t-tests: 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 only when compared to sham control values in the same animals. 2) CLON retarded and IDA accelerated kindling rate, defined as the number of 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 (n=0±SEM=0), whereas IDA provoked onset of spontaneous seizures in 100% of the animals (n=7±SEM=0) before or during the 5-week post-kindling follow-up during which seizures were provoked once each work day.Conclusions: 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.