Saffron (Crocus sativus L.) stigma reduces symptoms of morphine-induced dependence and spontaneous withdrawal in rats.

Background: Chronic morphine induces physical and psychological dependence signs. Saffron (Crocus sativus L.) stigma has been shown to have anxiolytic, antidepressant, and antinociceptive properties and to alleviate naloxone-precipitated withdrawal signs.Objectives: Therefore, this study was designed to examine the effects of saffron aqueous extract on the severity of physical-psychological dependence, voluntary morphine consumption, and the cerebrospinal fluid (CSF) serotonin levels following locomotor sensitization in morphine-dependent rats and in rats undergoing morphine withdrawal.Materials: Adult male rats were treated with morphine (10 mg/kg, sc twice daily) for 10 days. Rats received saffron extract (60 mg/kg, ip) daily, during the induction of morphine dependence and/or withdrawal. Then, rats were tested for spontaneous withdrawal signs, anxiety using the elevated plus-maze, depression using sucrose preference test, and voluntary morphine consumption using a two-bottle choice paradigm, and then challenged with morphine (1 mg/kg, ip) to evaluate of locomotor sensitization and CSF serotonin levels.Results: The results showed saffron extract during induction of morphine dependence decreased the severity of withdrawal signs (P = .05), while it had no effect on anxiety and depression-like behaviors. Saffron extract during morphine withdrawal exhibited an increase in the percentage (or ratio) of open/total arm entries (P = .017), higher levels of sucrose preference (P = .0001), a lower morphine preference ratio (P = .02) and also, a decrease in locomotor activity (P = .004) and an increase in the CSF serotonin levels (P = .041) in rats challenged to morphine.Conclusions: Saffron extract may exert a protective effect against morphine-induced behavioral sensitization in rats, probably through increasing serotonin levels.

A history of iron deficiency anemia during infancy alters brain monoamine activity later in juvenile monkeys.

Both during and after a period of iron deficiency (ID), iron-dependent neural processes are affected, which raises the potential concern that the anemia commonly experienced by many growing infants could have a protracted effect on the developing brain. To further investigate the effects of ID on the immature brain, 49 infant rhesus monkeys were evaluated across the first year of life. The mothers, and subsequently the infants after weaning, were maintained on a standardized diet containing 180 mg/kg of iron and were not provided other iron-rich foods as treats or supplements. As the infants grew, they were all screened with hematological tests, which documented that 16 (33.3%) became markedly ID between 4 and 8 months of age. During this anemic period and subsequently at 1 year of age, cerebrospinal fluid (CSF) specimens were collected to compare monoamine activity in the ID and iron-sufficient infants. Monoamine neurotransmitters and metabolite levels were normal at 4 and 8 months of age, but by 1 year the formerly anemic monkeys had significantly lower dopamine and significantly higher norepinephrine levels. These findings indicate that ID can affect the developmental trajectory of these two important neurotransmitter systems, which are associated with emotionality and behavioral performance, and further that the impact in the young monkey was most evident during the period of recovery.

[Effect of nociceptin on histamine and serotonin release in the central nervous system]. / A nociceptin hatása a hisztamin és szerotonin kiáramlásra a központi idegrendszerben.

Role in pain sensation of both nociceptin (NC), the bioactive heptadecapeptide sequence of preproorphaninFQ and of histamine has been widely evidenced in the central nervous system (CNS). In the current series of experiments effect of intracerebroventricularly (i.c.v.) administered NC (5.5 nmol/rat) on histamine and serotonin levels in blood plasma, CSF and brain areas (hypothalamus and hippocampus) was studies and compared to the effect of the mast cell degranulator Compound 48/80(100microg/kg, i.c.v.) and the neuroactive peptide Substance P (50nmol/rat, i.c.v.). It was found that all the three compounds increased the histamine level in the CNS, however their activity concerning the mast cell-, and neuronal histamine release is different. NC could release histamine from both the mast cells and the neurons and it decreased CNS serotonin levels. Substance P was found the most potent in increasing CNS histamine levels. Compound 48/80 treatment resulted in elevated histamine levels both in the CNS and blood plasma. It is concluded that the histamine releasing effects of i.c.v. administered NC and SP are limited to the CNS, but in the effect of Compound 48/80 its blood-brain barrier impairing activity is also involved. Data also demonstrate that NC has significant effect on both the histaminergic and serotonergic neurotransmission in the CNS.

Opposite changes in dopamine metabolites and met-enkephalin levels in the ventricular CSF of patients subjected to thalamic electrical stimulation.

High-frequency electrical stimulations of thalamic nuclei are currently used for the suppression of parkinsonian or essential tremor and for the relief of some types of intractable pain in man. However, the mechanisms by which such stimulations exert their therapeutic effects are essentially unknown. Attempts were made to provide some insight into these mechanisms by measuring the levels of the dopamine metabolites homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC), the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and met-enkephalin-like immunoreactivity in ventricular cerebrospinal fluid (CSF) of patients with Parkinson's disease (PD) or multiple sclerosis (MS) after a 30-minute therapeutic electrical stimulation of the ventralis intermedius nucleus of the thalamus. In nonstimulated control patients, the levels of these compounds did not significantly differ in two CSF samples taken 30 minutes apart. In stimulated patients, a decrease in dopamine metabolite levels associated with a relative increase in met-enkephalin-like immunoreactivity were observed in the CSF sample taken after the 30-minute stimulation as compared to the sample taken immediately before the stimulation. In contrast, the levels of 5-HIAA remained unaffected by the stimulation. These data confirmed the existence of negative interactions between dopaminergic and enkephalinergic systems in man similar to those previously demonstrated in rats. In addition, they suggest that alterations in dopaminergic or enkephalinergic neurotransmission might be involved in the therapeutic action of thalamic electrical stimulation in patients with parkinsonian symptoms and other patients.

[The participation of the serotonin link in the neurochemical mechanism of transcranial electroanalgesia]. / Uchastie serotoninovogo zvena v neirokhimicheskom mekhanizme transkranial'noi élektroanal'gezii.

Metergoline and 5, 7-dihydroxytryptamine were found to suppress and to prevent an electroanalgesic effect, resp. An increase in the serotonine contents in the CSF after electroanalgesia suggests an activation of the brain serotoninergic system. DL-5-hydroxytryptophan and allopurinol enhanced the electroanalgetic effect. The data obtained suggests an existence of a serotoninergic component of the transcranial electroanalgesia mechanism.

[Analysis of changes in serotonin, histamine, and prostaglandin E2 levels in cerebrospinal fluid and body tissues during hyperthermia of various origins]. / Analiz izmenenii soderzhaniia serotonina, gistamina i prostaglandina E2 v spinomozgovoi zhidkosti i tkaniakh organizma pri gipertermiiakh razlichnogo proiskhozhdeniia.

Physical hyperthermia caused distinct increase in content of serotonin in liquor and its decrease in hypothalamus of rabbits and rats, while histamine and PGE2 were unaltered in liquor of these animals. Considerable increase of PGE2 in liquor simultaneously with unaltered content of serotonin and histamine were detected in rabbits with pyrogenal-caused fever. A decrease in PGE2 content and elevation of serotonin were found in animals liquor after normalization of body temperature within 7 hrs of the pyrogenal treatment. The biogenic amines studied appear to serve as constituents of the natural antipyretic body system in animals, whereas PGE2 belongs to factors responsible for elevation of body temperature.

[Serotonin metabolism in patients with brain tumors]. / Obmen serotonina u bol'nykh s opukholiami golovnogo mozga.

In patients with brain tumours there was revealed an increase in the content of serotonin, 5-oxyindol acetic acid (5-OAA) and melatonin in the liquor, and of serotonin in the plasma rich with platelets. The content of serotonin or products of its metabolism in the liquor, as well as of serotonin in platelets depends on the involvement of truncus cerebri and hypothalamus in the pathologic process and on the gravity of the patient's condition. The serotonin content, in contrast to 5-OAA, s significantly higher in patients with tumours attended by epileptic attacks. The data obtained testify to a possible role of serotonin in the pathogenetic mechanisms of tumours development in the central nervous system.