Effects of Hemerocallis flava on motor activity and the concentration of central monoamines and its metabolites in rats.

In this study, we used behavioral and biochemical methods to investigate the effects of Hemerocallis flava (Liliaceae) (abbreviated as HF) on motor activity and the concentration of monoamines in rats. The water fraction of the resuspended HF extract was most active in reducing the motility in rats. The water fraction of the HF extract enhanced the reduction of locomotor activity produced by alpha-methyl-p-tyrosine and 5-hydroxytryptophan, but it reduced the increase of locomotor activity produced by L-dopa plus benserazide and p-chlorophenylalanine. Furthermore, the water fraction of the HF extract significantly decreased the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in the brain stem. It also increased the concentration of vanilylmandelic acid in the cortex, homovanillic acid and 5-hydroxyindole-acetic acid in the brain stem. These results suggest that the reduction of locomotor activity produced by the water fraction of HF extract may be related to the decrease in the concentration of norepinepherine in the cortex and the concentration of dopamine and serotonin in brain stem.

Regional differences in cerebral noradrenaline turnover in mice withdrawn from repeated morphine treatment and tolerance to the effects of acute morphine.

The effects of morphine withdrawal and challenge doses (10 or 30 mg/kg) on the alpha-methyl-p-tyrosine (alpha MT)-induced noradrenaline (NA) depletion as well as on the free 3-methoxy-4-hydroxyphenylethylene glycol (MOPEG) concentration were studied in various brain areas of NMRI mice. Morphine was given subcutaneously 3 times daily for 5 days followed by 1 or 3 days' withdrawal. In morphine withdrawn mice the alpha MT-induced NA depletion and the free MOPEG concentrations were differentially altered. At 1-day withdrawal the alpha MT-induced NA depletion was retarded and the NA concentration was elevated in the forebrain area indicating reduced release of NA. Simultaneously, however, the free MOPEG concentration was significantly elevated in the forebrain area and in the lower brain stem suggesting enhanced NA turnover. No withdrawal-induced changes were found in the hypothalamic NA turnover. Acute morphine elevated the free MOPEG concentration and accelerated the alpha MT-induced NA depletion in all brain areas of control mice but not in mice withdrawn for 1 day from repeated morphine treatment. At 3 days' withdrawal, however, the 30 mg/kg morphine dose slightly accelerated the NA depletion in the forebrain area. These results show that morphine withdrawal differentially alters the alpha MT-induced NA depletion and the free MOPEG concentration in various mouse brain areas. These effects are relatively modest suggesting that in mice the noradrenergic mechanisms play a minor role in morphine withdrawal syndrome. However, in all brain areas of the morphine-withdrawn mice tolerance was found towards the NA turnover and release accelerating effect of acute morphine.

Dopamine agonists potentiate antiakinetic effects of competitive NMDA-antagonists in monoamine-depleted mice.

The competitive NMDA-antagonists SDZ EAA-494 and CGP 37849 and the mixed D-1/D-2 dopamine agonists CI 201-678 and SDZ 205-152 reverse akinesia in monoamine-depleted mice in a dose dependent manner. Combination of threshold doses of NMDA-antagonists with dopamine agonists markedly enhances anti-akinetic effects. CI 201-678 which in addition to D-1 and D-2 receptors stimulates alpha-2 receptors produces a stronger effect than SDZ 205-152 which is devoid of alpha-2 agonist activity. The results indicate that concomitant blockade of NMDA-receptors and activation of dopamine receptors results in synergistic or at least additive motor stimulatory effects.

NMDA antagonists potentiate antiparkinsonian actions of L-dopa in monoamine-depleted rats.

Systemically administered N-methyl-D-aspartate (NMDA) antagonists, MK-801 ((+)5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) and CPP (3-[(+-)-2-carboxypiperazin-4-yl]-propyl-1-phosphonate), potentiate the ability of L-dopa (L-3,4-dihydroxyphenylalanine) to reverse akinesia and to alleviate muscular rigidity in monoamine-depleted rats. On the basis of these findings, it is proposed that NMDA antagonists may be beneficial as adjunctive treatment in the therapy of Parkinson's disease. CPP locally injected into the subthalamic nucleus, entopeduncular nucleus--the rat homologue of the internal pallidal segment--or substantia nigra pars reticulata of monoamine-depleted rats stimulates locomotor activity and alleviates rigidity, whereas local microinjection of CPP into the neostriatum is ineffective. These results make it unlikely that the neostriatum is the site of the antiparkinsonian action of NMDA antagonists in monoamine-depleted rats, whereas the subthalamic nucleus, internal pallidal segment, and substantia nigra pars reticulata appear to be important for the effects of NMDA antagonists.

Effect of alpha-methyl-p-tyrosine on neuroleptic-induced catalepsy in rat.

Pretreatment with alpha-methyl-p-tyrosine, a tyrosine hydroxylase inhibitor, was found to increase the intensity of catalepsy induced by haloperidol, chlorpromazine and molindone. The drug probably decreases the synthesis of dopamine and makes less dopamine available for release and to compete with the neuroleptic for the postsynaptic striatal dopamine receptor sites with resultant potentiation of the neuroleptic-induced catalepsy.

Different acute effects of the tyrosine hydroxylase inhibitors alpha-methyl-p-tyrosine and 3-iodo-L-tyrosine on hypothalamic noradrenaline activity and adrenocorticotrophin release in the rat.

Computerized gas chromatography-mass spectrometry techniques using selected ion monitoring and deuterated internal standards were used to assay simultaneously the medial basal hypothalamic concentrations of dopamine (DA) and noradrenaline (NA) and their major metabolites in individual rats 30 min after the administration of two different inhibitors of tyrosine hydroxylase, alpha-methyl-p-tyrosine (alpha-MT) and 3-iodo-L-tyrosine (MIT). Consistent with inhibition of DA synthesis, administration of both alpha-MT and MIT resulted in marked reductions (P less than 0.005) in the hypothalamic concentrations of DA and its metabolite homovanillic acid as well as in highly significant increases in prolactin secretion. alpha-MT administration, but not MIT, resulted in a highly significant decrease in NA concentration and a highly significant increase in the concentration of the NA metabolite 3,4-dihydroxyphenylethyleneglycol (DHPG). The hypothalamic ratio DHPG/NA was thus markedly increased (P less than 0.005) by alpha-MT indicating increased NA neuronal activity. alpha-MT administration also resulted in increased ACTH secretion (P less than 0.0005), an effect not observed following MIT. It is proposed that the effects on hypothalamic NA activity and ACTH secretion caused by alpha-MT are stress-mediated and unrelated to tyrosine hydroxylase inhibition. MIT is devoid of these effects but exhibits blockade activity, thus indicating it to be a preferable drug for the acute inhibition of tyrosine hydroxylase in neuroendocrine investigations.

Effects of aminergic drugs and glutamic acid on audiogenic seizures induced by early exposure to ethanol.

Adult C57BL/10Bg mice, normally resistant to audiogenic seizures, became susceptible when the mothers drank 10 per cent ethanol in water during pregnancy and for 14 days postpartem. Reserpine enhanced the incidence of seizures, and the effect was reversed by 5-hydroxytryptophan but not by dihydroxyphenylalanine. p-Chlorophenylalanine also enhanced the incidence of seizures, whereas alpha-methyl equals p equals tyrosine did not effect. Monsodium glutamate almost completely prevented seizures. These results are consistent with the interpretation that the serotonergic systems may be among those involved in the seizure mechanism induced by fetal and early exposure to ethanol.