Biomedical subjects

H Kuribara

Publications and source records attributed to H Kuribara.

At least 37 records · Page 2Linked to original sources

PubMed1998

[Prostate specific antigen doubling time in prostate cancer before treatment and in refractory status].

Prostate-specific antigen(PSA) increases exponentially in prostate cancer patients before treatment and in refractory status. PSA increases in 68-86% of prostate cancer patients before treatment, and that of the remaining 14-32% of the patients is stable. Those patients with a higher pre-treatment PSA level are more likely to have a shorter PSA-doubling time(PSA-DT). The relationship between pre-treatment stage, grade and PSA-DT is controversial. PSA-DT in biochemical failure patients predicts the risk of clinical recurrence. PSA-DT was correlated well with time to clinical recurrence after biochemical failure. Distant recurrence was associated with short PSA-DT. Higher clinical stage and lower differentiation before treatment correlated with shorter PSA-DT in recurrent cancer patients. PSA-DT is an important parameter for judging malignant potential of each cancer.

Biomarkers, Tumor↗

PubMed1998

[Evaluation of transition zone biopsy in systematic prostate biopsy].

We evaluated the systematic biopsies performed on 83 patients suspected of having prostate cancer. In the systematic biopsy, 6 cores were from the peripheral zone and 2 cores from the transition zone. Cancer was detected in 25 patients (30.1%). The percentage of patients who had abnormal digital rectal examination and transrectal echo findings, average PSA and PSA density, and the number of examinations which suggested cancer were higher in the cancer group than in the non-cancer group, although the mean prostate volume was smaller. Cancer was more frequently detected in the peripheral zone than in the transition zone. Cancer was detected only in the transition zone in only 1 of the 25 cancer patients. We conclude that biopsy of the transition zone to all the patients is not always needed in systematic biopsy.

Aged↗

PubMed1997

Memory disturbance and hippocampal degeneration induced by continuous intraventricular infusion of a protease inhibitor, leupeptin.

Effects of a protease inhibitor, leupeptin, on the memory function and the morphological changes in the hippocampus were examined in rats. The leupeptin was infused by an implanted-osmotic minipump into the lateral ventricle of the rats for 14 days. The acquisition and the maintenance of memory were evaluated by a step-down passive avoidance task. The control rats, infused with an artificial cerebral spinal fluid, showed good retention for the passive avoidance training for 21 days after training. The leupeptin-treated rats showed good retention for 7 days following training; however, pronounced impaired retention was observed on day 10 and thereafter. These rats were accompanied by a degeneration of the dentate gyrus in the histological examinations on Days 14 and 21. The granule cells in the dentate gyrus of the hippocampus appeared much more eosinophilic pyknotic. Numerous eosinophilic spherical structures of the cell processes were seen in the neuropil beneath the granule cell layer. Electron microscopic examination disclosed a marked accumulation of lipofuscin-like granules in the perikaryon of the cells and in the dendrites and the axons. These findings suggest that the memory impairment is closely related to the degeneration of the dentate gyrus in the hippocampus in the leupeptin-treated rats.

Animals↗

PubMed1997

Effects of tetrabenazine on methamphetamine-induced hyperactivity in mice are dependent on order and time-course of administration.

The ambulation-increasing effect of methamphetamine (MAP: 2 mg/kg s.c.) in mice persisted for about 3 h. Tetrabenazine (TBZ: 4 mg/kg s.c.), a depleter of monoamines from the cytoplasmic pool did not increase ambulation on its own. Pretreatment with TBZ at 1.5 h before administration of MAP inhibited the stimulant effect of MAP. In contrast, combined administration of two drugs resulted in a transient but considerable enhancement of MAPs stimulant effect. Post-MAP treatment with TBZ at 0.5-2 h hardly modified MAPs behavioral effects. In contrast, 3-6 h post-MAP treatment with TBZ induced a transient increase in activity, although the stimulant effect of MAP had already disappeared. The maximum increase in ambulatory stimulation was produced by 4-h post-MAP treatment with TBZ. The inhibitory effect of TBZ pretreatment on MAP-induced hyperactivity, as well as the transient hyperactivity elicited by TBZ when administered along with MAP, or 4 h after MAP, was dose-dependent. Preliminary studies revealed that transient hyperactivity was never produced by combination of GBR-12909 (a selective dopamine reuptake inhibitor) with TBZ or MAP with oxypertine (a selective norepinephrine releaser/depleter), but produced by combination of nialamide (a monoamine oxidase inhibitor) with TBZ. Inhibition of MAPs effects by TBZ pretreatment suggests that enhancement of dopamine release from cytoplasmic pool, and inhibition of dopamine reuptake by MAP, are involved in MAPs acute behavioral effects. Further, the fact that neither TBZ administration following GBR-12909 pretreatment, nor oxypertine treatment following MAP pretreatment, elicited transient hyperactivity suggests that dopamine is involved in hyperactivity elicited by post-MAP treatment with TBZ. It is also suggested that inhibition of monoamine oxidase (MAO) by MAP and dopamine displacement by TBZ may be responsible for the transient stimulation produced by 3-6 h post-MAP treatment with TBZ. It is hypothesized that the MAO inhibitory action of MAP persists after cessation of its acute stimulant effect, possibly up to 6 h after administration.

Adrenergic Uptake Inhibitors↗

PubMed1997

Effects of postmethamphetamine treatment with restraint on ambulatory sensitization to methamphetamine in mice.

The administration of methamphetamine (2 mg/kg SC) to mice was followed by acceleration of ambulation (locomotion) for 3 h, with the peak effect at 1/2-1 h. When mice were allowed free ambulation for 3 h in an activity cage of 20 cm in diameter after methamphetamine administration, repeated administrations of methamphetamine, four times at 3-day intervals, caused ambulatory sensitization; the count at the fourth administration being approximately 2.3 times as high as that at the first administration. Furthermore, the mice that were allowed ambulation in the activity cage during postmethamphetamine period of either 0-1/2, 0-1, 0-2, or 1/2-1 h (during the other periods, the mice were put in jars of 6 cm in diameter to restrict ambulation) demonstrated ambulatory sensitization to methamphetamine, and these levels were as same as that in the mice given methamphetamine with free ambulation for 3 h. However, the free ambulation during postmethamphetamine periods of 0-1/4 h and 1-3 h failed to produce strong sensitization to methamphetamine. These results suggest that a free ambulation for at least 1/2 h during the postmethamphetamine period of 0-1 h is important for induction of ambulatory sensitization to methamphetamine in mice.

Animals↗

PubMed1997

Assessment of the anxiolytic and amnesic effects of three benzodiazepines, diazepam, alprazolam and triazolam, by conflict and non-matching to sample tests in mice.

The anti-conflict and amnesic effects of three benzodiazepines (diazepam, alprazolam and triazolam) po-administered in mice were assessed by a modified Geller Seifter conflict test and a non-matching to sample test using a 4-arm maze with 3 selectable arms, respectively. Diazepam (10 mg/kg), alprazolam (1-10 mg/kg) and triazolam (1 and 3 mg/kg) significantly increased the lever-press in the alarm period (punished responding) under the conflict test. Under the non-matching to sample test, the correct response (CR), but not non-reward response (NR), decreased depending on the delay time. Diazepam (3 mg/kg) significantly decreased the CR under 0-sec delay condition, but not that under 30-sec delay condition. Comparatively higher doses of the benzodiazepines, diazepam (10 mg/kg), alprazolam (1 and 3 mg/kg) and triazolam (0.3 and 1 mg/kg), significantly decreased the CR under both 0- and 30-sec delay conditions. However, no significant change in the NR was produced by any dose of the three benzodiazepines. These results suggest that the decrease in CR during the non-matching to sample test is caused by the impairment of cognitive function rather than working and reference memories, and that such effects appear at doses equal to and/or less than the effective doses for anti-conflict effect. However, the assumption that triazolam has the highest risk of induction of amnesia, as compared to the advantage of sleep induction or relief of anxiety in the benzodiazepine group, was not supported by the present results.

Alprazolam↗

PubMed1996

Effects of interdose interval on ambulatory sensitization to methamphetamine, cocaine and morphine in mice.

To determine the minimum interdose interval for induction of ambulatory sensitization to methamphetamine, cocaine and morphine, 3 sets of 5 groups of mice were treated with either methamphetamine (2 mg/kg s.c.), cocaine (10 mg/kg s.c.) or morphine (10 mg/kg s.c.) 3 times at intervals of 3, 6, 12, 24 or 48 h, and then 2 times at intervals of 3 days in all groups. During the first 3 administrations of both methamphetamine and cocaine, interdose intervals of 3-12 h did not produce a significant change in the ambulatory stimulation. However, 3 repeated administrations of morphine with interdose intervals of 3 and 6 h, but not 12 h, caused tolerance to the ambulatory stimulant effect. The administration of all drugs with interdose intervals of 24 and 48 h produced ambulatory sensitization. Furthermore, following the fourth and fifth administrations of each drug, all groups of mice demonstrated sensitization. These results indicate that an interdose interval of 24 h or longer is required for induction of ambulatory sensitization to methamphetamine, cocaine and morphine.

Animals↗

PubMed1996

Effect of haloperidol on the behavioral stimulation by N-cyanomethylmethamphetamine, a main product of smoking methamphetamine mixed with tobacco.

N-Cyanomethylmethamphetamine is a main product of smoking methamphetamine mixed with tobacco. The aim of this experiment was to evaluate the effects of haloperidol on behavioral stimulation by N-cyanomethylmethamphetamine (3 mg/kg s.c.) in terms of ambulation in mice. Repeated administration of N-cyanomethylmethamphetamine, carried out 5 x at 3-day intervals, induced a sensitization to its ambulation-increasing effect. Haloperidol (0.01, 0.03, 0.1 and 0.3 mg/kg s.c.) significantly inhibited not only the acute stimulant effect of N-cyanomethylmethamphetamine but also the induction of sensitization. The dose-effect curves for the inhibitory effects of haloperidol on the N-cyanomethylmethamphetamine-induced ambulatory stimulation were almost the same between the drug-native and N-cyanomethylmethamphetamine-sensitized mice. Moreover, such behavioral characteristics of N-cyanomethylmethamphetamine; the behavioral stimulant effect, the induction of sensitization following repeated administration, and the inhibition of its effects by haloperidol, were qualitatively the same as those of methamphetamine (2 mg/kg s.c.). These results suggest that N-cyanomethylmethamphetamine possesses methamphetamine-like central stimulant effect and that D2 dopaminergic mechanisms are involved in the effect of N-cyanomethylmethamphetamine.

Amphetamines↗

PubMed1996

Importance of post-drug environmental factors for induction of sensitization to the ambulation-increasing effects of methamphetamine and cocaine in mice.

Mice given five repeated administrations of methamphetamine (MAP: 2 mg/kg SC) or cocaine (COC: 20 mg/kg SC) at 3-day intervals in a round tilting-type activity cage (20 cm in diameter) showed sensitization to the ambulation-increasing effect of each drug. The mean 3- or 2-h overall activity count at the fifth administration of MAP or COC, respectively, was 2.3-2.5 times higher than that at the first administration. Mice given MAP or COC 4 times in round spaces (15-30 cm in diameter), where the floor did not tilt, exhibited sensitization as strong as that demonstrated by mice given each drug in the activity cages, when the mice were given the fifth administration in the activity cages. In contrast, mice repeatedly given the drugs in spaces 4-9 cm in diameter never, and those in space 12 cm in diameter only partially, exhibited sensitization to MAP and COC. Furthermore, mice given MAP or COC 4 times in their home cages (25D x 20W x 15H cm, with ten mice in each cage) showed partial sensitization. Repeated administration of saline to mice in activity cages, in the spaces 4-30 cm in diameter, or in the home cages did not cause significant change in the sensitivity to either MAP or COC. These results suggest that repeated experience of the stimulant effect of drug and the resultant ambulation is required for induction of sensitization to MAP and COC in terms of ambulation in mice. It is also suggested that spaces larger than 12 cm in diameter, which correspond to 2-2.5 times as long as the body length without tail, and no interference from other mice are required for induction of strong sensitization to both MAP and COC.

Animals↗

PubMed1996

Interval-dependent inhibition of morphine sensitization of ambulation in mice by post-morphine treatment with naloxone or restraint.

The ambulation-increasing effect of morphine (10 mg/kg SC) persisted for approximately 3 h with a peak effect at around 1 h after the administration. This was examined on four occasions at 3-day intervals. Thus, treatment regimen-induced sensitization and the 3-h overall activity in the fourth administration was about 1.7 times higher than that in the first administration. Post-morphine treatments with naloxone (1 mg/kg SC) at 0 (i.e., simultaneously with) to 30 min after each morphine administration almost completely inhibited the induction of morphine sensitization. However, post-morphine treatments with naloxone at 1 h and later had no such inhibitory effect. Similarly, physical restriction of the ambulation of mice for 3 h (restraint), by putting them in a jar (6 cm in diameter, and 15 cm in height) inhibited the induction of morphine sensitization when restrain was started 0-30 min after each administration of morphine. Restraint starting 1 h and later did not alter the morphine sensitization. Post-morphine treatment with saline at any times did not change morphine sensitization. Furthermore, repeated administration of saline alone, naloxone alone, and saline with naloxone post-treatment or restraint did not change the sensitivity to morphine. These results clearly indicate that free ambulation for at least 1 h after the administration of morphine, i.e., the latency to reach the peak effect, is required completely to induce sensitization to morphine in terms of ambulation in mice.

Animals↗

PubMed1996

Inhibitory effect of restraint on induction of behavioral sensitization to methamphetamine and cocaine in mice.

Repeated intermittent (generally 3-day intervals) administrations of methamphetamine (MAP: 2 mg/kg, SC) or cocaine (COC: 20 mg/kg, SC) induced sensitization to the ambulation-increasing effect of individual drug in mice. The induction of MAP and COC sensitization was inhibited when restraint of the mouse (putting the mouse in a jar of 6 cm in diameter for 3 and 2 h after administration of MAP and COC, respectively) was started immediately after each drug administration. Furthermore, the induction of sensitizations to MAP and COC was significantly reduced when the restraint was started within 1/4 h and 1/6 h after the administration of MAP and COC, respectively, whereas the restraint starting thereafter did not affect the induction of sensitization. The three times repeated administrations of saline with or without restraint did not significantly change the sensitivities to MAP and COC. The ambulation-increasing effects of MAP and COC reached the peak at approximately 2/3 and 1/2 h, respectively, and persisted for 3 and 2 h after the administration. The present results suggest that, to completely induce sensitization to MAP and COC in terms of ambulation, the mice must freely move for at least half of the latency to their peak effects.

Animals↗

PubMed1996

Regulation of phospholipase D by low molecular weight GTP-binding proteins.

Phospholipase D (PLD) is believed to play an important role in cell signal transduction: PLD catalyzes the hydrolysis primarily of phosphatidylcholine (PC) to produce phosphatidic acid that may serve as a lipid second messenger. Although the mechanism of PLD activation has not yet been fully understood, a member of the low molecular weight GTP-binding protein (small G protein) superfamily, ADP-ribosylation factor (ARF), has been identified as a PLD-activating factor. In addition to ARF, we found that RhoA, another member of the small G proteins, activated rat brain PLD, and that ARF and RhoA synergistically stimulated the enzyme activity. When proteins of bovine brain cytosol were subjected to anion exchange column chromatography and then reconstituted with rat brain PLD partially purified from the membranes, fractions eluted at 60 mM NaCl, where ARF was not detected, activated the enzyme in a guanosine 5'-O-(3-thiotriphosphate)-dependent manner. This PLD-stimulating activity seemed to be attributed to a small G protein RhoA. Evidence provided includes the findings that: (1) the partially purified preparation of the PLD-activating factor by subsequent column chromatographies contained a 22 kDa substrate for botulinum C3 exoenzyme ADP-ribosyltransferase; (2) the 22 kDa protein strongly reacted with anti-RhoA antibody; (3) the treatment of the partially purified PLD-activating factor with C3 exoenzyme and NAD together, but not individually, significantly inhibited the PLD-stimulating activity; and (4) recombinant isoprenylated RhoA activated the PLD. On the contrary, recombinant nonisoprenylated RhoA failed to activate the PLD. Interestingly, the partially purified PLD-activating factor and ARF synergistically activated rat brain PLD, and recombinant isoprenylated RhoA could substitute for the partially purified preparation. These results conclude that rat brain PLD is regulated by RhoA in concert with ARF, and that the post-translational modification of RhoA is essential for its function as the PLD activator.

Animals↗

PubMed1996

Partially purified RhoA-stimulated phospholipase D activity specifically binds to phosphatidylinositol 4,5-bisphosphate.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is absolutely required for the ADP-ribosylation factor-stimulated phospholipase D (PLD) activity. In the present study, partially purified rat brain PLD was found to be activated by another PLD activator, RhoA, when PIP2, but not other acidic phospholipids, was included in vesicles comprising phosphatidylethanolamine (PE) and the PLD substrate phosphatidyicholine (PC) (PE/PC vesicles), demonstrating the absolute requirement of PIP2 for the RhoA-stimulated PLD activation, too. It is interesting that the RhoA-dependent PLD activity in the partially purified preparation was drastically decreased after the preparation was incubated with and separated from PE/PC vesicles containing PIP2. The PLD activity was extracted by higher concentrations of NaCl from the vesicles containing PIP2 that were incubated with and then separated from the partially purified PLD preparation. These results demonstrate that RhoA-dependent PLD binds to PE/PC vesicles with PIP2. The degree of binding of the RhoA-dependent PLD activity to the vesicles was totally dependent on the amount of PIP2 in the vesicles and correlated well with the extent of the enzyme activation. Further-more, it was found that a recombinant peptide of the pleckstrin homology domain of beta-adrenergic receptor kinase fused to glutathione S-transferase, which specifically binds to PIP2, inhibited the PIP2-stimulated, RhoA-dependent PLD activity in a concentration-dependent manner. From these results, it is concluded that in vitro rat brain PLD translocates to the vesicles containing PIP2, owing to its specific interaction with PIP2, to access its substrate PC, thereby catalyzing the hydrolysis of PC. PLD appears to localize exclusively on plasma membranes of cells and tissues. An aminoglycoside, neomycin, that has high affinity for PIP2 effectively extracted the RhoA-dependent PLD activity from rat brain membranes. This indicates that PIP2 serves as an anchor to localize PLD on plasma membranes in vivo.

ADP-Ribosylation Factors↗

PubMed1996

Age-dependent induction and maintenance of sensitization to methamphetamine-induced hyperactivity in mice.

Repeated administrations of methamphetamine (2 mg/kg, s.c.), 10 times at 3-day intervals, induced ambulatory sensitization in all groups of mice that were 13-, 15-, 19-, 23- and 36-week-old at the start of methamphetamine administration. The most prominent sensitization was observed in the 19-week-old mice. Among five groups of mice, even though the mice of 36 weeks old showed the highest sensitivity to methamphetamine at the first administration, they exhibited the lowest sensitization during the latter stage of repeated methamphetamine administration. Methamphetamine sensitization once established was well reproduced by the post-sensitization period of 8 weeks. Furthermore, the group of mice given methamphetamine with post-sensitization interval of 8 weeks (19-week-old mice) exhibited further enhancement of the sensitization. In contrast, the groups of mice given methamphetamine with post-sensitization intervals of 12 and 25 weeks (the 23- and 36-week-old, respectively) showed a significant reduced sensitization, and the latter group failed to reach the level of sensitization previously established. These results suggest that the induction of and maintenance of methamphetamine sensitization are dependent on the age of the mice, and that methamphetamine sensitization once established completely persists for up to 8 weeks.

Age Factors↗

PubMed1996

Characteristics of behavioural stimulant effect of N-cyanomethylmethamphetamine, a main product of smoking methamphetamine mixed with tobacco: evaluation by ambulatory activity in mice.

N-cyanomethylmethamphetamine is main product of smoking methamphetamine HCl (CAS code value: 537-46-2, molar mass: 185.70 g/mol) mixed with tobacco, and has a central stimulant action. The aims of this study were to assess in terms of ambulation in mice whether repeated administration of N-cyanomethylmethamphetamine HCl (molar mass: 211.70 g/mol) induced sensitization to its central stimulant effect, and whether there were cross-sensitization from N-cyanomethylmethamphetamine HCl to methamphetamine HCl, and from methamphetamine HCl to N-cyanomethylmethamphetamine HCl. N-cyanomethylmethamphetamine HCl 14.2 and 47.2 mumol/kg subcutaneously dose-dependently accelerated ambulation of mice. Five administrations at 3 day intervals caused sensitization, the activity counts in the fifth administration being approximately 2.6 and 1.6 times, higher respectively, than those in the first administration. Furthermore, the mice repeatedly given 14.2 and 47.2 mumol/kg N-cyanomethylmethamphetamine HCl exhibited cross-sensitization to methamphetamine HCl (10.8 mumol/kg subcutaneously). Whereas 1.4 and 4.7 mumol/kg N-cyanomethylmethamphetamine HCl did not induce significant acceleration of the ambulation throughout the 5 repeated administrations, nor cross-sensitization to methamphetamine HCl. On the other hand, the 5 repeated administrations of methamphetamine HCl (10.8 mumol/kg) also caused sensitization to its ambulation-increasing effect, and the activity count in the fifth administration attained approximately 2.0 times higher than that in the first administration. The mice given methamphetamine HCl demonstrated cross-sensitization to 1.42-14.2 mumol/kg N-cyanomethylmethamphetamine HCl. Haloperidol (CAS code value: 52-86-8, molar mass: 375.88 g/mol; 0.027-0.80 mumol/kg subcutaneously) dose-dependently reduced the ambulation-increasing effects of N-cyanomethylmethamphetamine HCl and methamphetamine HCl in the drug-naive, and N-cyanomethylmethamphetamine HCl- and methamphetamine HCl-sensitized mice. These dose-effect relationships were similar between groups. The present results suggest that N-cyanomethylmethamphetamine HCl has a behavioural stimulant effect almost similar to that of methamphetamine HCl.

Amphetamines↗

PubMed1996

Differential effects of morphine-6-glucuronide, an active metabolite of morphine, and morphine on locomotor activity in mice: involvement of the opioid receptor.

Subcutaneous administration of morphine (2.5 to 20 mg/kg) or an active metabolite of morphine, morphine-6-glucuronide (2.5 to 20 mg/kg), increased the locomotor activity of mice in a dose-dependent manner. Fifteen mg/kg of morphine and 20 mg/kg of morphine-6-glucuronide were almost equipotent. Subcutaneous administration of the universal opioid antagonist, naloxone, but not the delta-selective antagonist, naltrindole, significantly suppressed the hyperlocomotion induced by morphine (15 mg kg). On the other hand the subcutaneous administration of relatively higher doses of naloxone or naltrindole significantly reduced the hyperlocomotion induced by morphine-6-glucuronide (20 mg/kg). These findings suggest that agonistic actions at the opioid receptors, especially at the delta- and mu-receptors, contribute to the morphine-6-glucuronide-induced hyperlocomotion.

Animals↗

PubMed1996

Effects of sulpiride and nemonapride, benzamide derivatives having distinct potencies of antagonistic action on dopamine D2 receptors, on sensitization to methamphetamine in mice.

The acute ambulatory stimulation by methamphetamine (2 mg kg-1 S.C.) was dose-dependently reduced by 3-h pretreatment or combined treatment with sulpiride (1-100 mg kg-1 S.C.), and combined treatment with nemonapride (0.003-0.03 mg kg-1 S.C.), benzamide derivatives having selective antagonistic action on dopamine D2 receptors. The repeated (5 times) administrations of methamphetamine at 3-day intervals induced a sensitization to its ambulation-increasing effect, and the sensitization was significantly inhibited by 3-h pretreatment with either sulpiride (10-100 mg kg-1), or combined treatment with either sulpiride (3 or 10 mg kg-1) or nemonapride (0.01 or 0.03 mg kg-1) at each methamphetamine administration. Although the ambulation-increasing effect of methamphetamine disappeared by 3 h after the administration, the 3-h post-treatment with sulpiride (3 mg kg-1) or nemonapride (0.03 mg kg-1) after each methamphetamine administration was effective for a significant inhibition of the induction of methamphetamine sensitization, whereas, the comparatively higher doses of sulpiride (30 and 100 mg kg-1 in the combined treatment, and 10-100 mg kg-1 in the post-treatment) did not inhibit the methamphetamine sensitization. On the other hand, the repeated administrations of sulpiride (30 and 100 mg kg-1) alone, but not any doses of nemonapride, at 3-day intervals elicited a significant increase in the sensitivity to methamphetamine. These results suggest that, although the potencies of the anti-methamphetamine effects of sulpiride and nemonapride differ by a factor of 3000, they inhibit the induction of sensitization to methamphetamine in the pretreatment, combined treatment and early post-treatment schedules. However, it is also suggested that the repeated treatment with comparatively higher doses of sulpiride may produce a denervation supersensitivity of dopamine D2 receptors, and resultant increase in the sensitivity to methamphetamine.

Animals↗

PubMed1996

Modification by MK-801 (dizocilpine), a noncompetitive NMDA receptor antagonist, of morphine sensitization: evaluation by ambulation in mice.

The effects of five administrations (3- to 4-day intervals) of morphine (MOR: 10 and 20 mg/kg, s.c.) alone, MK-801 (dizocilpine: 0.03, 0.1, 0.3 and 1 mg/kg, i.p.) alone, and combinations of MOR with MK-801 on the ambulation in mice were investigated. MK-801 at 0.3 and 1 mg/kg, but not at 0.03 and 0.1 mg/kg, significantly increased the ambulation of mice. Although the mice given repeated administrations of MK-801 (0.3 and 1 mg/kg) exhibited enhancement and reduction, respectively, in the ambulation-increasing effect of the individual doses, they showed significantly higher sensitivity than the saline-treated mice to the challenge with MOR (10 mg/kg). The repeated administrations of MOR (10 and 20 mg/kg) induced a progressive enhancement of the ambulation-increasing effect. The mice repeatedly given MOR (10 mg/kg) exhibited significant increase in the sensitivity to MK-801 (0.03-0.3 mg/kg). The coadministrations of MOR with MK-801 intensified the ambulation-increasing effect, and repeated coadministrations induced progressive enhancement of the effect, except for the combinations of MOR (10 or 20 mg/kg) with MK-801 (1 mg/kg). However, the induction of MOR sensitization was not modified by any doses of MK-801, except for the case of combination of MOR (20 mg/kg) with MK-801 (1 mg/kg) which was highly toxic (i.e., eliciting death or a moribund condition). On the other hand, simultaneous treatment with SCH 23390 (0.05 mg/kg, s.c.) or nemonapride (0.05 mg/kg, s.c.), or 4-hr pretreatment with reserpine (1 mg/kg, s.c.) strongly, and 4-hr pretreatment with alpha-methyl-p-tyrosine (200 mg/kg, i.p.) partially reduced the ambulation-increasing effect of both MOR (10 mg/kg) and MK-801 (0.3 mg/kg). Simultaneous treatment with naloxone (1 mg/kg, sc) selectively reduced the effect of MOR. However, simultaneous treatment with apomorphine (0.1 mg/kg, s.c.) did not modify the effects of either drug. These results suggest that the characteristics of the ambulation-increasing effects of MOR and MK-801 are similar to each other, and that the repeated treatments with MK-801 induce a cross-sensitization to MOR and vice versa.

Animals↗