Methamphetamine-induced Stereotyped Behavior Research Articles

Pretreatment with CHIR-99021, a GSK-3 inhibitor, partially attenuates methamphetamine-induced stereotyped behavior in mice

Pretreatment with CHIR-99021, a GSK-3 inhibitor, partially attenuates methamphetamine-induced stereotyped behavior in mice

Neuropeptide S attenuates methamphetamine-induced stereotyped behavior in rats

Effective therapies for Methamphetamine (METH) induced stereotyped behavior are still being explored. It is unclear whether Neuropeptide S (NPS) is involved in the mechanism of METH-induced stereotyped behavior. In the contemporary behavioral study, pretreatment with NPS reduces stereotyped circling significantly, but didn’t have any impact on the total incidence of stereotypy and stereotyped sniffing and biting induced by METH (10 mg/kg). When METH (10 mg/kg) was administered to rats, the level of NPS in the cerebrospinal fluid was not affected, but pretreatment with NPS reversed METH-induced glutamate release in the hippocampus and striatum. The findings suggest that NPS receptor system is likely to involve in the METH-overdose-induced behaviors.

The ethyl acetate fraction of a methanolic extract of unripe noni (Morinda citrifolia Linn.) fruit exhibits a biphasic effect on the dopaminergic system in mice.

In earlier ex vivo studies, we reported the biphasic effect of a methanolic extract of unripe Morinda citrifolia fruit (MMC) on dopamine-induced contractility in isolated rat vas deferens preparations. The present in vivo study was designed and undertaken to further explore our earlier ex vivo findings. This study examined the effect of the ethyl acetate fraction of a methanolic extract of unripe Morinda citrifolia Linn. fruit (EA-MMC; 5–100 mg/kg, p.o.) on the dopaminergic system using mouse models of apomorphine-induced climbing time and climbing behavior, methamphetamine-induced stereotypy (sniffing, biting, gnawing, and licking) and haloperidol-induced catalepsy using the bar test. Acute treatment with EA-MMC at a low dose (25 mg/kg, p.o.) significantly attenuated the apomorphine-induced climbing time and climbing behavior in mice. Similarly, EA-MMC (5 and 10 mg/kg, p.o.) significantly inhibited methamphetamine-induced stereotyped behavior in mice. These results demonstrated that the antidopaminergic effect of EA-MMC was observed at relatively lower doses (<25 mg/kg, p.o.). On the other hand, EA-MMC showed dopaminergic agonistic activity at a high dose (3,000 mg/kg, p.o.), which was evident from alleviation of haloperidol (a dopamine D2 blocker)-induced catalepsy in mice. Therefore, it is concluded that EA-MMC might possess a biphasic effect on the dopaminergic system, i.e., an antagonistic effect at lower doses (<25 mg/kg, p.o.) and an agonistic effect at higher doses (>1,000 mg/kg, p.o.). However, further receptor-ligand binding assays are necessary to confirm the biphasic effects of M. citrifolia fruit on the dopaminergic system.

Pretreatment or Posttreatment with Aripiprazole Attenuates Methamphetamine-induced Stereotyped Behavior in Mice

Aripiprazole is a third-generation atypical antipsychotic and a dopamine D2 receptor partial agonist. In the present study, we investigated whether a single administration of aripiprazole to mice, either as a pretreatment or as a posttreatment, would affect stereotypy induced by methamphetamine (METH). Pretreatment of male ICR mice with aripiprazole (1 or 10 mg/kg, i.p.) attenuated the incidence of METH-induced stereotypical behavior in a dose-dependent manner. Pretreatment of mice with 1 mg/kg aripiprazole produced an increase in the locomotor activity in mice treated with METH compared with mice treated with vehicle plus METH and with 10 mg/kg aripiprazole plus METH. This increase in locomotion is indicative of a rightward shift in the dose–response curve for METH, consistent with a shift in the type of stereotypical behavior observed from biting to sniffing. Aripiprazole posttreatment, after METH-induced stereotypical behavior, was fully expressed and also significantly attenuated overall stereotypy in an aripiprazole dose-dependent manner. These data suggest that the antagonism of METH effects by aripiprazole should be investigated as a potential treatment for acute METH overdose.

P-211 - Effect of diabetes on methamphetamine-induced stereotyped behavior in rats

P-211 - Effect of diabetes on methamphetamine-induced stereotyped behavior in rats

Competitive and non-competitive N-methyl-D-aspartate antagonists fail to prevent the induction of methamphetamine-induced sensitization

In order to elucidate the possible roles of the glutamate system in the mechanisms underlying behavioral sensitization, which is used as an animal model for human psychosis, we investigated the effects of 3-((±)-2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) and MK-801 ((+)-dizocilpine), a competitive and non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, respectively, on methamphetamine-induced behavioral sensitization in rats. Administration of 0.5 mg/kg MK-801 enhanced 2 mg/kg methamphetamine-induced hyperactivity, whereas it reduced 6 mg/kg methamphetamine-induced stereotyped behavior markedly. CPP (10 mg/kg) reduced 2 mg/kg methamphetamine-induced stereotypy slightly. Repeated treatment with 2 and 6 mg/kg methamphetamine alone induced progressive augmentation of stereotypy, whereas combining either MK-801 or CPP with methamphetamine treatment abolished or attenuated this augmentation. However, when rats were challenged with methamphetamine after a 7-day period of abstinence, the intensity of stereotypy among the rats pretreated with repeated doses of methamphetamine alone or in combination with MK-801 or CPP did not differ significantly. These results indicate that competitive and non-competitive NMDA receptor antagonists modulate acute methamphetamine-induced abnormal behavior and sensitization expression, but they failed to prevent the induction of the neural mechanisms underlying behavioral sensitization.

Effects of quinidine and cimetidine on methamphetamine stereotypy in rats.

The effects of quinidine and cimetidine on methamphetamine-induced stereotyped behavior were studied in rats. Quinidine (10, 30 and 50 mg/kg) and cimetidine (100, 250 and 500 mg/kg) were administered orally 60 min prior to subcutaneous injection of a fixed dose of methamphetamine (5 mg/kg). It was found that quinidine and cimetidine very markedly potentiated the intensity of methamphetamine stereotypy. The duration of the stereotypy in the group pretreated with either drug was 2.3-4.0 times longer than that in the control group. Furthermore, the urinary pH levels of rats were measured after administrations of methamphetamine alone and of methamphetamine following the drugs in question. Urinary pH was not changed by pretreatments with those drugs, suggesting that the enhancing effects of quinidine and cimetidine on methamphetamine-induced stereotyped behavior are not derived from a change in urinary pH level. The enhancement of methamphetamine-induced stereotyped behavior may be explained by inhibitory effects of quinidine and cimetidine on the metabolism of methamphetamine.

Studies on the mechanism of interaction between methamphetamine and quinine in rats.

Interactions between methamphetamine and quinine were studied using two different tests. The duration and intensity of methamphetamine-induced stereotyped behavior was enhanced by pretreatment of rats with quinine. Pretreatment of rats with SKF-525A and CCl4 also resulted in the enhancement of methamphetamine-induced stereotyped behavior. Pretreatment with phenobarbital shortened the stereotypy evoked by methamphetamine. Furthermore, urinary excretion patterns of methamphetamine and its metabolites were determined following the administration of the drug to rats which had been pretreated with certain drugs. Quinine, SKF-525A and CCl4 inhibited the urinary excretion of p-hydroxylated metabolites and increased the excretion of the unchanged methamphetamine and amphetamine. These results strongly suggest that the enhancement of methamphetamine-induced stereotyped behavior in the rats pretreated with quinine, SKF-525A and CCl4 could be ascribed to the inhibition of the p-hydroxylation reaction of methamphetamine and thus may lead to the increased concentration and pharmacological effect of the drug.

Enhancement of Behavioral Effect and Acute Toxicity of Methamphetamine by Qu nine in Rats

The behavioral effect and acute toxicity of methamphetamine were tested alone and in combination with quinine in rats. Quinine prolonged and increased the effect of methamphetamine. The enhancement of methamphetamine-induced stereotyped behavior was very marked when quinine was given prior to or simultaneously with methamphetamine. Flowever, the time for onset of methamphetamine-induced stereotyped behavior was not affected by quinine. The mortality of methamphetamine was also potentiated markedly by quinine. The enhancement of the behavioral effect and the toxicity of methamphetamine may be due to inhibition of the metabolism of methamphetamine by quinine.

Studies on drug dependence (Report 99): Effect of quinine on methamphetamine-induced stereotyped behavior and acute toxicity in rats

It has been reported that quinine(Q) can improve the methamphetamine(MA)-induced anorexia in rats. In the present experiments, the effects of Q on MA-induced stereotyped behavior (SB) and acute toxicity were examined. MA was injected s.c.,and Q was given p.o. For SB observation, fixed doses of MA(5 mg/kg) and Q(50 mg/kg) were used, and rats were divided into 4 groups as follows: l.MA alone; 2.Q, 60 min before MA; 3.MA and Q administered at the same time; 4.MA, 60 min prior to Q. They were observed continuously after MA administration, and the latency of onset, duration and intensity of SB were recorded for 8 hr. For studies on acute toxicity, various doses of MA or each in combination with a fixed dose(50 mg/kg) of Q were tested. Deaths were recorded for 3 days after drug administration. The MA-induced SB was found to be potentiated in all of the treatment combined with Q. The intensity and duration of SB in the group administered MA and Q at the same time was similar to Q pretreatment and more potent than that in the group given MA prior to Q. However, onset of SB did not change in when MA was given alone or in combination with Q. The lethality of MA was significantly increased in the group given MA combined with Q. These results suggest that Q can enhance the MA-induced SB and acute toxicity. It may be explained by the influence on the metabolic rate for MA.

Small doses of apomorphine induce catalepsy and antagonize methamphetamine stereotypy in rats.

Small doses of apomorphine (AP, 31.25-125 micrograms/ kg IP) induced dose-dependent catalepsy in rats. However, unlike the stereotyped behavior induced by high doses of AP which has a rapid onset and is short-lasting, the cataleptic effect induced by small doses of AP was evident 30 min after AP injection and was unusually long-lasting. Further, AP (31.25-125 micrograms/kg) administered 60 min before methamphetamine was found to significantly antagonize the methamphetamine-induced stereotyped behavior. Pretreatment with molindone (0.45 and 0.8 mg/kg IP), in doses reported to selectively block the presynaptic DA receptors, not only decreased the cataleptic effect of AP but also reversed the AP antagonism of methamphetamine stereotypy. The results suggest that small doses of AP induce catalepsy and antagonize methamphetamine stereotypy probably by an action at presynaptic DA receptor sites.

Effect of drugs influencing central serotonergic mechanisms on methamphetamine-induced stereotyped behavior in the rat.

Pretreatment with L-tryptophan, a precursor of serotonin, was found to decrease the intensity of stereotyped behavior induced by methamphetamine, while methysergide, a serotonin antagonist, was found to increase the intensity of methamphetamine-induced stereotyped behavior. These results suggest that the intensity of methamphetamine-induced stereotypy depends on the balance between central dopaminergic and serotonergic systems and that the central serotonergic system may have an opposing, tonic effect upon central dopaminergic systems involved in the mediation of stereotypy. In contrast to L-tryptophan, however, pretreatment with quipazine, a serotonin agonist, and clomipramine, a selective, serotonin neuronal uptake blocker, was found to potentiate the stereotyped behavior induced by methamphetamine. The probable mechanisms by which quipazine and clomipramine might have potentiated the methamphetamine-induced stereotypy are discussed.

4) - Effects of penfluridol and other drugs on methamphetamine-induced stereotyped behavior in monkeys

4) - Effects of penfluridol and other drugs on methamphetamine-induced stereotyped behavior in monkeys

Influence of adrenalectomy on emotional behavior and brain methamphetamine concentration in rats--effect of chronic administrations of ACTH

The authors studied, in two experimental periods (spring and summer), the influence of adrenalectomy or chronic administrations of ACTH on methamphetamine-induced stereotyped behavior (sniffing, biting and licking) and increase of brain amphetamine level in rats. In both spring and summer, the brain amphetamine levels were markedly increased in adrenalectomized rats. Within the limits of the spring experiment, the biting hehavior was not observed in rats which had been treated with ACTH, while the frequent appearance of sniffing behavior in adrenalectomized rats was inhibited by ACTH. Within the limits of the summer experiment, the licking behavior was not seen in rats treated with ACTH, while the lack of biting in adrenalectomized rats was restored with administration of the drug.