Paul R. Farber

Monoamines and sleep: microdialysis findings in pons and amygdala

This is the first microdialysis report comparing concentrations (pg/microliter) of norepinephrine (NE), serotonin (5-HT) and dopamine (DA) derived from feline locus ceruleus complex (LC) and amygdala. NE and 5-HT declined progressively from waking to slow-wave-sleep (SWS) and then to rapid-eye-movement (REM) sleep. Concentrations of DA did not change at either collection site across the sleep-wake cycle. We conclude that release of NE and 5-HT release modulates physiologic components related to the sleep-wake cycle, but DA does not.

Monoamines and seizures: microdialysis findings in locus ceruleus and amygdala before and during amygdala kindling

We used microdialysis to determine extracellular concentrations of norepinephrine (NE), dopamine (DA) and serotonin (5-HT) before and during a 1-day amygdala kindling paradigm. Subjects were young cats (<1 year old; n=8; 6 female, 2 male). Consecutive 5-min samples (2 microl/min infusion rate) were obtained from left amygdala and ipsilateral locus ceruleus complex (LC) under 3 experimental conditions lasting 1-h each (n=12 samples per cat per condition): (1) just before amygdala stimulation (baseline), (2) during focal afterdischarge (AD) and (3) during generalized AD. ADs were elicited by electrical stimulation applied to establish thresholds immediately before dialysate collection as well as during each sample collected in focal vs. generalized AD conditions. Sample concentrations were time-adjusted to correspond with sleep vs. waking state and/or focal vs. generalized ADs. Seizure activity was indexed by AD threshold (mA) and duration (s) as well as number and duration of specific clinically evident (behavioral) seizure manifestations. Main results were: (1) Lower baseline concentrations (fmoles per sample) of NE, DA and 5-HT correlated with subsequent increases in duration of focal and generalized AD as well as number of behavioral seizure correlates. (2) When compared to baseline levels, NE, DA and 5-HT concentrations significantly increased only in amygdala during focal AD and in both amygdala and LC during generalized AD. (3) NE and 5-HT concentrations were higher than DA at both collection sites and were selectively associated with increased wakefulness throughout the study.

The α2-adrenoreceptor agonist clonidine suppresses seizures, whereas the α2-adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens : A comparison of amygdala and pontine microinfusion effects

Summary: Purpose: We sought to determine whether local, in vivo microinfusion of an α2‐adrenoreceptor agonist and antagonist into either the amygdala or the pons (locus ceruleus, LC) would have contrasting effects on evoked amygdala‐kindled seizure susceptibility.

The α2 adrenoreceptor agonist clonidine suppresses seizures, whereas the α2 adrenoreceptor antagonist idazoxan promotes seizures: Pontine microinfusion studies of amygdala-kindled kittens

Abstract This is the first report showing that microinfusion of α2 adrenoreceptor agonists and antagonists into the vicinity of the locus ceruleus (LC) have contrasting effects on evoked amygdala-kindled seizure susceptibility. Microinfusions (1 μ1) of the α2 agonist clonidine (CLON) and of the α2 antagonist idazoxan (IDA) were made over 1 min through cannulae in the LC ipsilateral to the kindled amygdala in 6 kittens. Order of administered drugs (CLON vs. IDA) and dosages (n = 3 each were partly counterbalanced. Focal and convulsive seizure thresholds were evaluated 10–12 min post-infusion and compared to thresholds obtained during two, interspersed control conditions (vehicle control = 1 μ1 microinfusion of sterile saline; sham control = needle insertion only). CLON significantly elevated focal and generalized seizure thresholds, whereas IDA significantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose-dependent. These findings confirm that norepinephrine (NE) is a potent antiepileptic agent. Results also suggest that pontine microinfusions could eventually provide an alternative treatment option for medically refractory limbic epilepsy.

Developmental Temporal Lobe Epilepsy in Amygdala Kindled Kittens: An update

In 1990, we published the first report of amygdala kindling in kittens and the first description of a spontaneous seizure model in immature animals.3 We found that spontaneous epilepsy was more likely to occur after amygdala kindling in preadolescents than in adults and that the post-kindling onset was most rapid in the youngest animals. This update is intended to fill some gaps in the initial report on the ontogeny of temporal lobe epilepsy.4

Ontogeny of Temporal Lobe Epilepsy in Amygdala-Kindled Kittens

This chapter addresses three topics. First, we depict the features of a unique developmental model of spontaneous temporal lobe epilepsy (TLE) in amygdala-kindled kittens. Second, we report recent advances in potential treatment alternatives via focal and extra-focal microinfusion of anti-epileptic agents as well as mechanisms which could explain them. Third, we suggest mechanisms that could account for the spontaneous increase in seizure discharge propagation during non-rapid-eye-movement (NREM) sleep, including the transition into rapid-eye-movement (REM).