The effect of clonidine on cell survival, glutamate, and aspartate release in normo- and hyperglycemic rats after near complete forebrain ischemia.

The present study was undertaken to investigate the effects of the alpha2 adrenergic agonist, clonidine, on the near complete cerebral ischemia (NCFI) evoked release of glutamate and aspartate from normo- and hyperglycemic rodent brain tissue using microdialysis tissue techniques. Hemodynamic variables, blood lactate, and glucose levels were monitored throughout the 40 min NCFI occlusion period. After 48 h, rats were killed and the extent of neuronal injury was determined in the cortex, striatum, and hippocampus.

Agonist-induced serotonin 2A receptor desensitization in the rat frontal cortex and hypothalamus.

This study examined the time course and possible mechanisms of agonist-induced desensitization of 5-hydroxytryptamine serotonin 2A receptors in the rat frontal cortex and hypothalamic paraventricular nucleus after 1, 4, and 7 days of treatment with (-)-1-(2,5-dimethoxy-4-iodophenyl)2-aminopropane HCl [(-)-DOI] (1 mg/kg i.p.), a selective 5-HT(2A/2C) receptor agonist.

Chronic fluoxetine differentially affects 5-hydroxytryptamine (2A) receptor signaling in frontal cortex, oxytocin- and corticotropin-releasing factor-containing neurons in rat paraventricular nucleus.

Differential adaptive changes in serotonin2A [5-hydroxytryptamine (5-HT)2A] receptor signaling during treatment may be one mechanism involved in the latency of therapeutic improvement with antidepressants, such as fluoxetine. We examined the effects of fluoxetine (2, 3, 7, 21, or 42 days) on hypothalamic 5-HT2A receptor signaling. The hormone responses to an injection of the 5-HT2A receptor agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-amino-propane HCl (DOI) were used as an index of hypothalamic 5-HT2A receptor function.

Neuroendocrine evidence that (S)-2-(chloro-5-fluoro-indol- l-yl)-1-methylethylamine fumarate (Ro 60-0175) is not a selective 5-hydroxytryptamine(2C) receptor agonist.

The 5-hydroxytryptamine(2A) and (2C) (5-HT(2A) and 5-HT(2C)) receptors are so closely related that selective agonists have not been developed until recently with the advent of (S)-2-(chloro-5-fluoro-indol-l-yl)-1-methylethylamine fumarate (Ro 60-0175), a putatively selective 5-HT(2C) receptor agonist. In the present study, Ro 60-0175 was used to analyze the importance of 5-HT(2C) receptors in hormone secretion. Injection of Ro 60-0175 (5 mg/kg s.

Cerebrospinal fluid free choline in movement disorders of paediatric onset.

We measured free choline in cerebrospinal fluid (CSF) of 78 patients with movement disorders of paediatric onset and various controls as a putative index of central phospholipid metabolism. Most of the disorders studied were myoclonic disorders, such as progressive myoclonus epilepsy, the opsoclonus-myoclonus syndrome, and essential myoclonus, but other movement disorders, interictal seizure disorders, and different neurological and nonneurological disorders were also included. There were no significant differences in CSF choline concentrations in myoclonic disorders or other movement disorders compared with controls.

Mivazerol inhibits intrathecal release of glutamate evoked by halothane withdrawal in rats.

Background: Mivazerol is a new and selective alpha 2-adrenergic receptor agonist devoid of hypotensive effects (1, 2). Previous studies have demonstrated that mivazerol prevents hemodynamic instability during emergence from halothane anesthesia in rats (3). The present study was to determine whether glutamate and aspartate are involved in this action of mivazerol, at the second to third thoracic segments (T2-T3) of the spinal cord.

Effects of immobilization stress on hippocampal monoamine release: modification by mivazerol, a new alpha 2-adrenoceptor agonist.

Mivazerol is a new and selective alpha 2-adrenoceptor agonist which has demonstrated anti-ischemic effects, both in animals and in patients with myocardial ischemia. In the present study, mivazerol was evaluated for its ability to inhibit the release of catecholamines and serotonin (5-HT) in the hippocampus of freely moving rats, and also was compared to clonidine. In vivo microdialysis in combination with high-performance liquid chromatography (HPLC) was employed.

Methyl-beta-carbolinium analogs of MPP+ cause nigrostriatal toxicity after substantia nigra injections in rats.

Eleven beta-carbolinium compounds (beta C+s) and MPP+ were stereotaxically injected (40-200 nmol in 5 microliter of vehicle) unilaterally into the substantia nigra of anesthetized adult male Sprague-Dawley rats. The rats were sacrificed after three weeks. The ipsilateral striatum was analyzed for dopamine and DOPAC levels with HPLC.

Comparison of the effects of natural and synthetic huperzine-A on rat brain cholinergic function in vitro and in vivo.

(-)-Huperzine-A has been shown to be a promising agent for the treatment of dementia of the Alzheimer type. This substance is rare in nature. We have been able to prepare a racemic mixture of (+/-)-huperzine-A in quantity.

Long-term exposure to high levels of corticosterone aggravates AF64A-induced cholinergic hypofunction in rat hippocampus in vivo.

Male Sprague-Dawley rats were bilaterally adrenalectomized and corticosterone (CORT) was substituted as subcutaneous pellets in two groups of animals: low- (L-CORT: 1 x 25 mg pellet) or high-level of CORT (H-CORT: 4 x 100 mg pellet). Between 14 and 19 days after CORT substitution, ethylcholine aziridinium (AF64A) was intracerebroventricularly (i.c.

Natural and synthetic Huperzine A: effect on cholinergic function in vitro and in vivo.

Huperzine A has been shown to be useful in the treatment of symptoms of dementia of the Alzheimer type. Our initial attempts to synthesize (-)Huperzine A resulted in the racemic mixture of (+/-)Huperzine A. We have therefore compared the in vitro and in vivo effects of (+/-)Huperzine A with those of (-)Huperzine A in rats.

Sex differences and estrous cycle-variations in the AF64A-induced cholinergic deficit in the rat hippocampus.

The influence of gender and stage of the estrous cycle on the levels of acetylcholine, serotonin, and noradrenaline in the hippocampus and on the susceptibility of the cholinergic septo-hippocampal pathway to the neurotoxic effect of ethylcholine aziridinium (AF64A) was investigated in the rat. Levels of acetylcholine and serotonin were consistently higher in female rats during the stage of diestrus and proestrus than in age-matched male rats (p < 0.05).

Septal choline acetyltransferase immunoreactive neurons: dose-dependent effects of AF64A.

Two experiments were performed. In the first, the cholinotoxin, AF64A (0.5, 1.

Inhibition of high affinity choline transport attenuates both cholinergic and non-cholinergic effects of ethylcholine aziridinium (AF64A).

Ethylcholine aziridinium (AF64A) has been proposed as a specific cholinergic neurotoxin. In earlier studies, using AF64A, we reported that slow infusion of 1-2 nmol of this compound into each lateral ventricle of Sprague-Dawley rats resulted in small, and transient decreases in noradrenaline (NA) and serotonin (5-HT) levels in the hippocampus, while inducing a permanent and significant cholinergic hypofunction in the same brain region. The experiments described in this paper were designed to test the hypothesis that such noradrenergic and serotonergic changes after small doses of AF64A are secondary to the changes observed in cholinergic neurons.

Clonidine prevents transient loss of noradrenaline in response to cholinergic hypofunction induced by ethylcholine aziridinium (AF64A).

Intracerebroventricular injection of ethylcholine aziridinium (AF64A) (2 nmol/ventricle) induced a considerable decrease in the level of acetylcholine (ACh) in hippocampus (from 21.14 +/- 0.84 to 10.

Noradrenaline depletion protects cholinergic neurons in rat hippocampus against AF64A-induced damage.

The role of the noradrenergic system in the cholinotoxicity of ethylcholine aziridinium ion (AF64A) was studied in rats. Male Sprague-Dawley rats were treated with the noradrenergic neurotoxin DSP-4 (N-(2-chloroethyl)-n-ethyl-2-bromobenzylamine; 50 mg/kg i.p.

Modulation of smooth muscle responses by serine proteases and related enzymes.

Standard isolated smooth muscle tissue preparations were used to screen the musculotropic actions of serine proteases and other substances that are generated during hemostatic activation. Sera obtained from human, rabbit, and guinea pigs produced a dose-dependent contraction of these isolated tissue preparations. These sera also augmented the actions of epinephrine and other agonists on different tissue preparations.

Metabolism of choline in brain of the aged CBF-1 mouse.

In order to quantify the changes that occur in the cholinergic central nervous system with aging, we have compared acetylcholine (Ach) formation in brain cortex slice preparations from 2-year-old aged CBF-1 mouse brains and compared the findings with those in 2-4-month-old young adult mouse brain slices. Incorporation of exogenous radioactively labelled choline (31 nM [3H] choline) into acetyl choline in incubated brain slices was linear with time for 90 min. Percentage of total choline label distributed into Ach remained constant from 5 min after starting the incubation to 90 min.

Inhibition of bradykinin-induced contraction of isolated smooth muscle tissue preparations by oligopeptide thiobenzyl ester substrates for serine proteases.

Synthetic peptide substrates containing various chromophores and fluorophores have been utilized in the quantitation of serine protease activities. Recently, amino acid thiobenzyl esters containing arginine and lysine have also been used to evaluate the serine proteases. In an attempt to develop specific peptide thiobenzyl substrates, we have screened D-Pro-Phe-Arg-S-CH2-C6H5, D-Phe-Phe-Arg-S-CH2-C6H5, D-Gly-Pro-Arg-S-CH2-C6H5, and D-Val-Leu-Lys-S-CH2-C6H5 to determine the enzymatic activity of serine proteases.

Inhibition of the contractile action of bradykinin on isolated smooth muscle preparations by derivatives of low molecular weight peptides.

The carbonyl terminal tripeptide sequence of bradykinin (Pro-Phe-Arg) is molecularly manipulated to obtain agents with potent antagonistic activity towards the smooth muscle contractile activity of bradykinin. Screening of various peptide derivatives revealed that heptyl amides or esters of H-D-Pro-Phe-Arg, and H-D-Phe-Phe-Arg possessed relatively stronger antibradykinin activity on the isolated smooth muscle preparation. The parent tripeptides, H-D-Pro-Phe-Arg-OH, and H-D-Phe-Phe-Arg-OH, and their amino acid components, i.