Monoaminergic uptake in synaptosomes prepared from frozen brain tissue samples of normal and narcoleptic canines.

Canine narcolepsy, a model of the human disorder, is associated with altered catecholamine but not serotonin (5-HT) metabolism in some brain areas, particularly the amygdala. A possible explanation for these global changes could be the existence of specific defects in monoamine uptake processes. We have studied the uptake of [3H]norepinephrine (NE), [3H]dopamine (DA) and [3H]5-HT in synaptosomes prepared from cortex and amygdala of narcoleptic and control Doberman pinscher brains.

Dopamine D2 mechanisms in canine narcolepsy.

Narcolepsy is a sleep disorder characterized by abnormal manifestations of rapid-eye-movement (REM) sleep and excessive daytime sleepiness. Using a canine model of the disease, we found that central D2 antagonists suppressed cataplexy, a form of REM-sleep atonia occurring in narcolepsy, whereas this symptom was aggravated by D2 agonists. The effect on cataplexy was stereospecific for the S(-) enantiomer of sulpiride (a D2 antagonist) and the R(+) enantiomer of 3-PPP (a D2 agonist).

Platelet alpha 2 adrenoceptors in human and canine narcolepsy.

We have recently established that canine narcolepsy (an autosomal recessive genetic model of the human disorder) is dramatically improved by treatment with alpha 2 antagonists such as yohimbine (Nishino et al: J Pharmacol Exp Ther 253:1145-1152, 1990). To further investigate the role of alpha 2 adrenoceptors in narcolepsy, receptors labeled with [3H] yohimbine were examined on platelets from human and canine narcoleptic subjects. Twenty-eight Doberman pinschers were studied, 7 controls (C), 7 heterozygous (Hz), and 14 narcoleptics (N) (age and sex matched), including eight animals born in a backcross setting (narcoleptic x heterozygous; 5 narcoleptics and 3 heterozygous).

Reduced affinity of peripheral benzodiazepine binding sites in elderly insomniac patients.

Peripheral-type benzodiazepine binding sites on intact platelets from untreated chronic insomniac patients and those chronically treated with benzodiazepine hypnotics were investigated to evaluate their putative involvement in sleep pathology and the influence of treatment. There were 34 elderly subjects in the study, 14 controls (80.7 years) and 20 insomniac patients, of whom 7 were untreated (61.

Binding sites for a peripheral type benzodiazepine antagonist ([3H]PK 11195) in human iris.

Peripheral-type benzodiazepine binding sites have been characterized on sections of 8 normal human iris/ciliary-body preparations. Saturability was determined at 25 degrees C with [3H] PK 11195 (1 nM) a specific ligand of peripheral type sites. The studies revealed a single class of binding sites for PK 11195 with a nanomolar range affinity (KD = 1.