Nobufumi Ono

Modifications by lithium of behavioral responses to methamphetamine and tetrabenazine

Different groups of mice were injected s.c. daily with lithium chloride in three doses (0.52, 1.58 and 4.72meq/kg) or with saline for a period of 3 weeks. Lithium administered acutely or chronically did not affect spontaneous locomotor activities. However, methamphetamine-induced hyper-locomotor activities were inhibited in the lithium groups as compared with those in the saline group, while the hyper-locomotor activities induced by tetrabenazine in the nialamide-pretreated animals were reduced to some extent but not significantly by lithium. Tetrabenazine brought about an initial transient increase followed by a decrease of spontaneous locomotor activities in the lithium groups, whereas it induced only a decrease of the activities in the saline group. In addition, jumping and vertical jumping behaviors, which were not observed in the saline group, occurred 30–60 min after tetrabenazine in the lithium groups. These effects of lithium tended to increase with an increase of the doses administered and with a prolongation of its daily administration. The results demonstrate that lithium modifies behavioral responses to methamphetamine and tetrabenazine.

Influences of cyclooxygenase inhibitors on the cataleptic behavior induced by haloperidol in mice

Haloperidol administered intraperitoneally, and prostaglandin F2 alpha (PGF2 alpha) and PGE2 intraventricularly induced dose-dependent cataleptic behavior in mice. The cataleptic behavior induced by haloperidol was inhibited dose-dependently by oral pretreatment with aspirin and indomethacin, inhibitors of PGs synthetase. Striatal 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindole 3 acetic acid (5-HIAA) were elevated by haloperidol, although dopamine (DA) and 5-hydroxytryptamine (5-HT) levels did not change. The increase of DOPAC level in striatum induced by haloperidol was significantly suppressed by aspirin, but not in brain stem. The alteration of DOPAC level by aspirin correlated with the behavioral response. These results suggest that central prostaglandin synthesis may participate in the development of cataleptic behavior, which might also involve alteration of brain catecholaminergic activity.

Possible involvement of prostaglandins in cataleptic behavior in rats

Involvement of prostaglandin (PG) in cataleptic behavior was investigated by a high bar test method in rats. PG F2 alpha (F2a) and E2 administered intracerebroventricularly (ICV) elicited cataleptic behavior in a dose-dependent manner. The cataleptic behaviors produced by PGs were markedly inhibited by ICV pretreatment with propranolol. The cataleptic behaviors induced by haloperidol were also inhibited by propranolol. The PG F2a- and haloperidol-induced cataleptic behaviors were almost abolished by the thermal coagulation of bilateral striatum where the dopaminergic and cholinergic link is found. The pilocarpine-induced cataleptic behavior was potentiated by ICV treatment with PG F2a. On the other hand, the cataleptic behavior elicited by haloperidol was reduced after oral treatment with aspirin, a PG synthesis inhibitor. These results suggest that PGs seem to be participated in incidence of cataleptic behavior, which might involve alteration of brain beta-adrenoceptor activity.

Release of plasminogen activator inhibitor-1 from human astrocytes is regulated by intracellular ceramide.

The present study underscores a regulatory role of intracellular ceramide in astrocytes for the release of an extracellular serine protease, tissue‐type plasminogen activator (t‐PA), and its inhibitor, plasminogen activator inhibitor‐1 (PAI‐1). Treatment of cultured human astrocytes with N‐acetylsphingosine, a cell‐permeable short‐chain ceramide analogue or daunorubicin that could increase intracellular ceramide via activation of ceramide synthase or sphingomyelin hydrolysis increased the release of t‐PA and conversely decreased the PAI‐1 release. Interestingly, treatment of the astrocytes with tumor necrosis factor (TNF)‐α also increased the intracellular ceramide levels but caused the elevation of PAI‐1 release without altering the t‐PA release. These data suggest that the generation of ceramide in astrocytes is linked at least with the regulation of PAI‐1 release. We also demonstrate that the suppression of PAI‐1 release with daunorubicin accelerates the cell death of neuronally differentiated PC12 cells and suggest an antiapoptotic role of PAI‐1 in the nervous system. J. Neurosci. Res. 62:781–788, 2000.

Central effects of taurine: antagonistic effects on central actions of angiotensin.

Renin released from the juxtaglomerular apparatus of the kidney into the circulation produces angiotensin (AT) and this compound increases tubular absorption of sodium and water, resulting in an increase in circulating blood volume. In addition, AT evokes a net increase in sympathetic vasoconstrictor activity. The presynaptic effect of AT facilitates adrenergic transmitter release (16) and may also involve increased transmitter synthesis (3) and inhibition of adrenergic uptake (21). The postsynaptic effect appears to be due to an increase in sensitivity to norepinephrine (24). Furthermore, large doses of AT exert a constrictive action in the smooth muscle of blood vessels. Thus, the role of the peripheral renin-AT system in regulating the blood pressure is significant.

Influences of β-blocking agents on cardiovascular actions induced by endothelin-3 administered intracerebroventricularly in anesthetized rats

Possible involvement that the pressor and positive chronotropic effects of endothelin-3 (ET-3) administered intracerebroventricularly (i.c.v.) participate in the central beta-adrenoceptor has been studied in urethane anesthetized rats. ET-3 administered i.c.v. at dose of 50 pmol elicited the increase in blood pressure and heart rate over a long duration, but a dose of 30 pmol had a minimal effect. These cardiovascular responses to ET-3 were significantly reduced by intravenous pretreatment with pentolinium, ganglionic blocking agent, and phentolamine, alpha-blocker. Also pressor responses to ET-3 were abolished dose-dependently by i.c.v. pretreatment with propranolol at a dose of 1 mumol, nonselective beta-blocker and ICI 118551, beta 2-selective adrenoceptor blocker, but not by i.c.v. pretreatment with metoprolol, atenolol, beta 1-selective blocker, procaine and phentolamine. These results suggest that ET-3 may play a role in cardiovascular regulation through the activation of the sympathetic nervous system involved in the central beta 2-adrenoceptor system.

Effect of aspirin on haloperidol-induced cataleptic behavior in mice

Haloperidol given intraperitoneally dose-dependently elicited cataleptic behavior, evaluated by high bar and four-cork tests, in mice. The haloperidol-induced cataleptic behavior was reduced dose-dependently after oral treatment with aspirin, a cyclooxygenase inhibitor. The intra-cerebroventricular administration of prostaglandin F2a produced cataleptic behavior of long duration determined by the high bar test. It is suggested that prostaglandins may participate in the induction of cataleptic behavior in part.

Role of the central muscarinic receptor of prostaglandin I2 in cardiovascular function in rat

The effects of injection of prostaglandin (PG) I2 into the cerebral ventricle on cardiovascular responses and their modification by intracerebroventricular (i.c.v.) pretreatment with several drugs were studied in male Wistar rats under urethane anesthesia. When injected into the ventricle, PG I2 (50 nmol/kg) caused a decrease in blood pressure and an increase in heart rate which were of short duration and were significantly inhibited by i.c.v. pretreatment with drugs, such as atropine (0.4 mumol/kg) and diphenhydramine (1 mumol/kg), having an anticholinergic effect. The similar effects induced by intravenous (i.v.) injection of PG I2 (5 nmol/kg) were not inhibited by i.v. pretreatment with these drugs. These results suggest that PG I2 play a role in regulation of cardiovascular function through central muscarinic acetylcholine receptors.

Central Effects of Prostaglandin F2α on the Cardiovascular System in the Rat

Effects on blood pressure and heart rate of prostaglandin (PG) F2α administered into a lateral cerebral ventricle (i.e.v.) were investigated in urethane anesthetized rats. PG F2α

The effect of neurotransmitters on cataleptic behavior induced by PG D2 in rats

The effects of several neurotransmitters on prostaglandin (PG) D2-induced cataleptic behavior in rats were investigated by the high bar test. Intracerebroventricular administration of PG D2 elicited cataleptic behavior in a dose-dependent manner without producing a marked change in spontaneous motor activity. The incidences of cataleptic behavior were 20% and 100% at doses of 2 nmol and 50 nmol of PG D2, respectively. Intraperitoneal pretreatment with L-DOPA (100 mg/kg), apomorphine (1 mg/kg), amantadine (0.2 mg/kg), atropine (0.5 mg/kg) or p-chlorophenylalanine (300 mg/kg) significantly decreased the cataleptic behavior induced by 50 nmol of PG D2. Conversely, simultaneous treatment with 5-hydroxy-L-tryptophan (30 mg/kg), 5-methoxy-N,N-dimethyltryptamine (5 mg/kg), imipramine (20 mg/kg) or clomipramine (10 mg/kg) markedly increased the cataleptic behavior induced by 2 nmol of PG D2. Propranolol (10 mg/kg) and phenoxybenzamine (10 mg/kg) did not affect the induction of cataleptic behavior by either 2 nmol or 50 nmol of PG D2. These results suggest that PG D2 might be involved in inducing cataleptic behavior by modulating serotonergic, cholinergic and dopaminergic systems.