The alpha 2-adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2-adrenoreceptor antagonist idazoxan promotes seizures in amygdala-kindled kittens: a comparison of amygdala and pontine microinfusion effects.

PURPOSE: We sought to determine whether local, in vivo microinfusion of an alpha 2-adrenoreceptor agonist and antagonist into either the amygdala or the pons (locus ceruleus, LC) would have contrasting effects on evoked amygdala-kindled seizure susceptibility. METHODS: The study population consisted of 6 amygdala-kindled kittens, each undergoing the same protocol, in which the amygdala microinfusion paradigm preceded the pontine microinfusion series. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulas adjacent to stimulating electrodes in the kindled amygdala or through cannulas adjacent to recording electrodes in the ipsilateral LC. Order of administered drugs (CLON vs. IDA) and dosages (n = 3 each) was partly counterbalanced. Focal and convulsive seizure thresholds were evaluated 10-12 min postinfusion and compared to thresholds obtained during two interspersed control conditions (vehicle control = 1 microliter microinfusion of sterile saline; sham control = needle insertion only). RESULTS: CLON significantly increased focal and generalized seizure thresholds, whereas IDA significantly reduced seizure thresholds when compared to controls. Magnitude of effects was dose dependent and more potent after pontine than amygdala microinfusion. CONCLUSIONS: Our results confirm and extent findings of previous researchers who used unlocalized in vivo manipulations to show that norepinephrine (NE) is a highly antiepileptic agent in the amygdala kindling preparation. With further investigation, the results may ultimately lead to development of microinfusion techniques as an alternative treatment option for limbic epilepsy.

The alpha 2 adrenoreceptor agonist clonidine suppresses seizures, whereas the alpha 2 adrenoreceptor antagonist idazoxan promotes seizures: pontine microinfusion studies of amygdala-kindled kittens.

This is the first report showing that microinfusion of alpha 2 adrenoreceptor agonists and antagonists into the vicinity of the locus ceruleus (LC) have contrasting effects on evoked amygdala-kindled seizure susceptibility. Microinfusion (1 microliter) of the alpha 2 agonist clonidine (CLON) and of the alpha 2 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 microliter 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.

The alpha 2-agonist clonidine suppresses seizures, whereas the alpha 2-antagonist idazoxan promotes seizures--a microinfusion study in amygdala-kindled kittens.

This is the first report showing that local, in vivo microinfusion of alpha 2-adrenoreceptor agonists and antagonists have contrasting effects on amygdala-kindled seizure susceptibility. Microinfusions (1 microliter) of the alpha 2-agonist clonidine (CLON) and of the alpha 2-antagonist idazoxan (IDA) were made over 1 min through cannulae adjacent to stimulating electrodes in five amygdala-kindled kittens. Order of administered drugs (CLON vs. IDA) and dosages (n = 3 each) was 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 microliter 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. Results confirm and extend previous findings which employed unlocalized, in vivo manipulations to show that norepinephrine is a potent antiepileptic agent in the amygdala kindling preparation.

The ontogeny of feline temporal lobe epilepsy: kindling a spontaneous seizure disorder in kittens.

We describe the ontogeny of feline temporal lobe epilepsy after amygdala kindling in 24 cats, aged 2.5 months to over 1 year. In so doing, we report the first experimental model of spontaneous epilepsy in immature animals. Preadolescent kittens (n = 12 less than or equal to 6.5 months) are far more likely to develop epilepsy, indexed by spontaneous seizures, than are adult cats (n = 12 greater than 1 year). Moreover, youth accelerated the development of epilepsy. The younger the kitten at the beginning of kindling, the more probable and rapid the onset of spontaneous seizures. Failed postictal depression was the most reliable precursor of spontaneous seizures in immature cats. However, spontaneous epilepsy continued after postictal refractory periods stabilized and was still present when kittens matured to adulthood. Collectively, the results suggest that failed inhibition contributes to the onset of spontaneous epilepsy in immature animals but that other morphologic, physiological and/or chemical changes might sustain epilepsy afterwards.

Thyrotrophin releasing hormone and related peptides in canine tissues.

Thyrotrophin releasing hormone (TRH)-immunoreactive peptides have been quantified in canine serum, hypothalamus, liver, pancreas, adrenal, thyroid, prostate, testis, epididymis and semen by TRH radioimmunoassay, SP-Sephadex C-25 cation exchange chromatography, Sephadex G-10 exclusion chromatography and high pressure liquid chromatography. The total concentration of TRH and TRH-like peptides was highest in the hypothalamus, followed by liver, adrenal, pancreas, thyroid, prostate, epididymis, testis and serum. All of the TRH immunoreactivity (TRH-IR) within extracts of the hypothalamus was due to TRH. On the other hand, nearly all of the TRH-IR of extracts of liver, thyroid, prostate, epididymis, testis and semen was due to TRH-homologous peptides. Adrenal and pancreatic extracts contained a greater proportion of TRH in relation to the TRH-homologous peptides. Extracts of dog serum and semen were found to contain a TRH-binding substance which reduced the retention of added TRH by cation exchangers. The half-time of disappearance (t1/2) of synthetic TRH incubated at 23 degrees C in 10% (w/v) homogenates in 0.15 M-NaCl-0.05 M-phosphate buffer, pH 7.5, ranged from 22 +/- 10 (S.D.) min for liver to 120 +/- 58 min for thyroid. The short t1/2 for TRH added to dog liver homogenates contrasted with a previous report that dog liver is essentially free of TRH-degrading activity.

Polymorphism at the glucosephosphate isomerase locus in the dog.

A polymorphism of the enzyme glucosephosphate isomerase (GPI) in canine red blood cells is reported. This polymorphism was detected by horizontal starch gel electrophoresis utilizing a tris-EDTA-borate buffer system of pH 8.0. Four out of 92 dogs examined appeared to be heterozygous at this locus.

Blood plasma levels of progesterone and oestradiol in the dog during the oestrous cycle and pregnancy.

Plasma oestradiol and progesterone levels were studied in German Shepherd and Greyhound bitches during the normal oestrous cycle, pregnancy and at parturition. The mean oestradiol level increased from approximately 7 to 13 pg/ml during the fifth week before onset of oestrus. Oestradiol stayed at this level until pro oestrus which was characterized by a steady increase to a mean peak level of about 30 pg/ml 5-6 days before oestrus. At the start of oestrus the level was approximately 12 pg/ml. A level between 10-15 pg/ml was kept during the following 10 weeks whether or not the bitch was pregnant and no change occurred at parturition. The mean progesterone level was found to be very low, around or under 1 ng/ml, until 1-4 days after the oestradiol peak after which the level gradually increased to around 10 ng/ml at the start of oestrus. During oestrus and metoestrus or pregnancy the pattern was inconsistent. In some bitches the level gradually increased during 3-4 weeks and reached a peak value of 30-50 ng/ml. The level then gradually decreased during 5-6 weeks. During the first 5 weeks of the same period progesterone in other bitches fluctuated between similar maximum levels and extremely low levels. After the fifth week the pattern was the same for all bitches. In the pregnant bitches there was a significant drop of the progesterone level at parturition. The data suggest that the dog is not an ideal test animal for steroids synthetized for use in man.