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PubMedDate not supplied

Methamphetamine use and HIV risk among substance-abusing offenders in California.

Recent epidemiological surveys of illicit substance use show a particularly high prevalence of methamphetamine use in the western and southwestern United States-most notably California. Moreover, in their analysis of 1995 Drug Use Forecasting data, Anglin and colleagues (1998) found that methamphetamine was a preferred substance among California arrestees. The present study uses data from 807 state prison inmates in California (32% of whom reported using methamphetamine prior to incarceration) to examine the associations between methamphetamine use and HIV risk behaviors. Methamphetamine users in this sample were significantly more likely than nonusers to have injected drugs during the six months prior to their current incarceration. Among injectors, however, injection-related risks (such as dirty needles and needle sharing, etc.) were not significantly associated with methamphetamine use. However, past six-month sex-related risks were dramatically higher for methamphetamine users. These patterns persisted even after controlling for background differences between the two groups. The results of this study underscore the importance of addressing the higher sex-related HIV/AIDS risk among methamphetamine users undergoing prison-based drug treatment.

Adult↗

PubMedDate not supplied

Epidemiology and public health Consequences of methamphetamine use in California's Central Valley.

Methamphetamine use is an increasingly serious public health problem in California and other parts of the country. Despite sensationalistic media attention, however, very little is known about users of this clandestinely consumed drug. Employing methods known as Rapid Assessment and Response, the authors describe the epidemiology and public health implications of methamphetamine use in California's Central Valley, with a focus on Sacramento, which many social indicators suggest has been more severely affected by methamphetamine than any city in the nation. Data sources for this report include interviews with drug users, statistical reports, epidemiologic studies, and local informed expert opinion. In their social demography, methamphetamine users in the Central Valley are in marked contrast to those of coastal cities such as Seattle and San Francisco, being largely heterosexual, and of mixed racial/ethnic heritage. Three-quarters or more initiate their use of the drug while still in their teens, with more than a quarter beginning use before the age of 15. Many of these rapidly gravitate to regular use, and continue using well into their thirties. Methamphetamine users are at much higher risk of infection with HIV than opiate users, particularly if they inject. Partly because methamphetamine enhances libido, users of the drug typically also have many more sexual partners. Not surprisingly, data indicate that methamphetamine users are more likely than heroin users to be HIV-infected. Methamphetamine appears to be less of a street drug than heroin, complicating efforts at street outreach. However, because it is typically used in social settings, a social or diffusion approach to HIV prevention might be particularly promising.

Amphetamine-Related Disorders↗

PubMed2005

Impacts of federal precursor chemical regulations on methamphetamine arrests.

AIMS: The US government regulated precursor chemicals, ephedrine and pseudoephedrine, multiple times to limit methamphetamine production/availability and thus methamphetamine problems. Research has found that the regulations reduced methamphetamine hospital admissions, but authors have argued that other problems were unaffected. This study examines whether the regulations impacted methamphetamine arrests. DESIGN: ARIMA-intervention time-series analysis with control series. SETTING: California (1982-2001). MEASUREMENTS: Dependent variable series: monthly methamphetamine arrests. Control series: monthly marijuana arrests and cocaine/heroin arrests. INTERVENTIONS: Bulk powder ephedrine and pseudoephedrine: regulated November 1989. Products containing ephedrine as the single active medicinal ingredient: regulated August 1995. Pseudoephedrine products: regulated October 1997. Large-scale producers used ephedrine and pseudoephedrine in these forms. Ephedrine combined with other active medicinal ingredients (e.g. various cold medicines)-used mainly by small-scale producers: regulated October 1996. FINDINGS: The regulation targeting small-scale producers (1996) had no significant impact. In contrast, methamphetamine arrests stopped rising and dropped 31% to 45% each of the three times precursor chemicals used by large-scale producers were regulated. Within 3 years of the bulk powder regulation (1989) and again within 2 years of the ephedrine single ingredient regulation (1995), arrests fully rebounded. During the 4 years following the last regulation (pseudoephedrine products, 1997) arrests only partially rebounded. These effects parallel those reported on hospital admissions. The control series were generally unaffected. CONCLUSIONS: Precursor regulations targeting large-scale producers impacted methamphetamine arrests, a criminal justice problem, much as they impacted the public health problem of methamphetamine hospital admissions. Ongoing research is needed to determine whether these problems eventually fully rebound from the last regulation.

California↗

PubMed1994

Up-regulation of neurotensin mRNA in the rat striatum after acute methamphetamine treatment.

The effect of acute subcutaneous administration of methamphetamine on the expression of neurotensin mRNA was investigated in the adult rat striatum. At different time points (2, 6 and 24 h) following drug administration rats were killed, and mRNA levels were quantified both on films and emulsion-dipped tissue sections from two striatal levels. Two hours after methamphetamine injection, a dramatic increase in neurotensin mRNA levels was detected in different areas of the striatum at both rostral and caudal levels. Numerous positive cells were observed in the dorsomedial, dorsolateral and ventrolateral parts of the striatum. This up-regulation reflected an increase both in the number of cells expressing neurotensin mRNA and in the mean mRNA levels. This increase was still present after 6 h and was similar to the 2 h treated group at the rostral level of the striatum, but lower at the caudal one. Twenty-four hours after methamphetamine injection, neurotensin mRNA levels were back to control values, or in some areas even below. A strong increase in neurotensin mRNA-expressing cells was also seen in the olfactory tubercle, and the time-course was similar to the one observed in the striatum. In a second set of experiments, the effect of methamphetamine was evaluated on adjacent striatal sections hybridized with probes directed against neurotensin and substance P mRNAs, respectively. Two hours after drug administration, a significant increase in the levels of both peptide mRNAs was observed (+190% for neurotensin, +80% for substance P). These results demonstrate that methamphetamine is able to induce a dramatic, rapid and transient increase in striatal neurotensin mRNA levels, which may partly account for the elevation in neurotensin peptide levels observed in the striatonigral pathway after methamphetamine. The different anatomical localization of neurotensin mRNA-expressing cells observed after haloperidol and methamphetamine treatments, as well as the fact that the D1 receptor antagonist SCH-23390 is able to counteract the effect of methamphetamine but not that of haloperidol on neurotensin mRNA expression, suggests that there are at least two different subpopulations of neurotensin cells in the striatum. One population is regulated via D1 receptors and projects to the substantia nigra pars reticulata. The second is sensitive to D2 receptor stimulation and may project to the globus pallidus and/or may represent interneurons.

Animals↗

PubMed1983

Involvement of presynaptic alpha 2-adrenoreceptors in the depressor response produced by repeated administration of dextro-methamphetamine.

The mechanism for the depressor response produced by the repeated administration of dextro-methamphetamine was studied in rats and rabbits. In the urethane anaesthetized and atropinized rat, the methamphetamine-induced depressor response was markedly inhibited by alpha-adrenoreceptor antagonists or by chronic reserpinization in combination with alpha-methyl-p-tyrosine, while it was not affected by propranolol. Yohimbine reversed the methamphetamine-induced depressor response to a pressor one when it was administered during the course of the depressor phase whilst prazosin or phentolamine caused only a further depressor response. In the pithed rat with electrical stimulation of the spinal cord, the first administration of methamphetamine elicited a marked pressor response whereas, following treatment with cocaine, the first administration of methamphetamine produced only a depressor response which was abolished by yohimbine. In the rabbit isolated aorta prelabeled with 3H-noradrenaline, methamphetamine enhanced the stimulation-evoked 3H-overflow and caused an enhanced contraction. However, in the presence of cocaine, methamphetamine reduced both stimulation-evoked 3H-overflow and neurogenic contractions. These findings suggest that the methamphetamine-induced depressor response results from the inhibition of catecholamine release from noradrenergic nerve terminals probably mediated by the activation of peripheral presynaptic alpha 2-adrenoreceptors.

Animals↗

PubMed2002

Ontogeny of neurokinin-1 receptor mediation of methamphetamine neurotoxicity in the striatum of the mouse brain.

We studied the role of the peptide substance P, signaling through the neurokinin-1 (NK-1) receptor, on methamphetamine-induced loss of dopamine transporter sites, a well-documented marker of toxicity in the striatum of the mouse brain, because this peptide is under dynamic regulation by the neurotransmitter dopamine. Methamphetamine is a psychostimulant that induces dopamine overflow from dopamine terminals of the striatum. Mice were given four injections of methamphetamine (7.5 mg/kg of body weight) at two-hour intervals and were sacrificed three days after the treatment. Dopamine transporter levels in the striatum were assessed by receptor autoradiography with [(125)I]RTI-121. Exposure to methamphetamine resulted in significant loss of dopamine transporters in the caudate-putamen. This loss was prevented by preexposure (30 min before the first injection of methamphetamine) of the neurokinin-1 receptor antagonist L-733,060. The inactive enantiomer of L-733,060 (L-733,061) failed to protect dopamine transporter sites from methamphetamine, suggesting specificity for the neurokinin-1 receptor. Moreover, the protective effect of L-733,060 was observed in mice that were 10 weeks of age or older (dopamine transporter sites in mice six and eight weeks old were not protected from methamphetamine by the neurokinin-1 receptor antagonist). The results demonstrate that the deleterious effect of methamphetamine on dopamine transporter sites of the striatum is mediated via the neurokinin-1 receptor. The involvement of the NK-1 receptor appears after the eighth week of postnatal life, suggesting that the link between dopamine transporters and the neurokinin-1 receptor becomes functional at approximately the time when the mouse reaches reproductive age.

Animals↗

PubMed2003

Methylphenidate alters vesicular monoamine transport and prevents methamphetamine-induced dopaminergic deficits.

It has been hypothesized that high-dose methamphetamine treatment rapidly redistributes cytoplasmic dopamine within nerve terminals, leading to intraneuronal reactive oxygen species formation and well characterized persistent dopamine deficits. We and others have reported that in addition to this persistent damage, methamphetamine treatment rapidly decreases vesicular dopamine uptake, as assessed in purified vesicles prepared from treated rats; a phenomenon that may contribute to aberrant intraneuronal dopamine redistribution proposedly caused by the stimulant. Interestingly, post-treatment with dopamine transporter inhibitors protect against the persistent dopamine deficits caused by methamphetamine; however, mechanisms underlying this phenomenon have not been elucidated. Also of interest are findings that dopamine transporter inhibitors, including methylphenidate, rapidly increase 1) vesicular dopamine uptake, 2) vesicular monoamine transporter-2 (VMAT-2) ligand binding, and 3) VMAT-2 immunoreactivity in a vesicular subcellular fraction prepared from treated rats. Therefore, we hypothesized that methylphenidate post-treatment might protect against the persistent striatal dopamine deficits caused by methamphetamine by rapidly affecting VMAT-2 and vesicular dopamine content. Results reveal that methylphenidate post-treatment both prevents the persistent dopamine deficits and reverses the acute decreases in vesicular dopamine uptake and VMAT-2 ligand binding caused by methamphetamine treatment. In addition, methylphenidate post-treatment reverses the acute decreases in vesicular dopamine content caused by methamphetamine treatment. Taken together, these findings suggest that methylphenidate prevents persistent methamphetamine-induced dopamine deficits by redistributing vesicles and the associated VMAT-2 protein and presumably affecting dopamine sequestration. These findings not only provide insight into the neurotoxic effects of methamphetamine but also mechanisms underlying dopamine neurodegenerative disorders, including Parkinson's disease.

Adrenergic Uptake Inhibitors↗

PubMed2005

Age-dependent methamphetamine-induced alterations in vesicular monoamine transporter-2 function: implications for neurotoxicity.

Tens of thousands of adolescents and young adults have used illicit methamphetamine. This is of concern since its high-dose administration causes persistent dopaminergic deficits in adult animal models. The effects in adolescents are less studied. In adult rodents, toxic effects of methamphetamine may result partly from aberrant cytosolic dopamine accumulation and subsequent reactive oxygen species formation. The vesicular monoamine transporter-2 (VMAT-2) sequesters cytoplasmic dopamine into synaptic vesicles for storage and perhaps protection against dopamine-associated oxidative consequences. Accordingly, aberrant VMAT-2 function may contribute to the methamphetamine-induced persistent dopaminergic deficits. Hence, this study examined effects of methamphetamine on VMAT-2 in adolescent (postnatal day 40) and young adult (postnatal day 90) rats. Results revealed that high-dose methamphetamine treatment caused greater acute (within 1 h) decreases in vesicular dopamine uptake in postnatal day 90 versus 40 rats, as determined in a nonmembrane-associated subcellular fraction. Greater basal levels of VMAT-2 at postnatal day 90 versus 40 in this purified fraction seemed to contribute to the larger effect. Basal tissue dopamine content was also greater in postnatal day 90 versus 40 rats. In addition, postnatal day 90 rats were more susceptible to methamphetamine-induced persistent dopaminergic deficits as assessed by measuring VMAT-2 activity and dopamine content 7 days after treatment, even if drug doses were adjusted for age-related pharmacokinetic differences. Together, these data demonstrate dynamic changes in VMAT-2 susceptibility to methamphetamine as a function of development. Implications with regard to methamphetamine-induced dopaminergic deficits, as well as dopamine-associated neurodegenerative disorders such as Parkinson's disease, are discussed.

Age Factors↗

PubMed2002

Persistent antagonism of methamphetamine-induced dopamine release in rats pretreated with GBR12909 decanoate.

Methamphetamine abuse is a serious global health problem, and no effective treatments for methamphetamine dependence have been developed. In animals, the addictive properties of methamphetamine are mediated via release of dopamine (DA) from nerve terminals in mesolimbic reward circuits. At the molecular level, methamphetamine promotes DA release by a nonexocytotic diffusion-exchange process involving DA transporter (DAT) proteins. We have shown that blocking DAT activity with high-affinity DA uptake inhibitors, such as 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl) piperazine (GBR12909), can substantially reduce amphetamine-induced DA release in vivo. In the present study, we examined the ability of a long-acting depot formulation of GBR12909 decanoate (GBR-decanoate) to influence neurochemical actions of methamphetamine in the nucleus accumbens of rats. Rats received single injections of GBR-decanoate (480 mg/kg i.m.) and were subjected to in vivo microdialysis testing 1 and 2 weeks later. Pretreatment with GBR-decanoate produced modest elevations in basal extracellular levels of DA, but not 5-hydroxytryptamine (5-HT), at both time points. GBR-decanoate nearly eliminated the DA-releasing ability of methamphetamine (0.3 and 1.0 mg/kg i.v.) for 2 weeks, whereas methamphetamine-induced 5-HT release was unaffected. Autoradiographic analysis revealed that GBR-decanoate caused long-term decreases in DAT binding in the brain. Our data suggest that GBR-decanoate, or similar agents, may be useful adjuncts in treating methamphetamine dependence. This therapeutic strategy would be especially useful for noncompliant patient populations.

Animals↗

PubMed2025

A genome-wide association study of methamphetamine use among people with HIV.

BACKGROUND: Amphetamine-like stimulants are the most used psychostimulants in the world; methamphetamine use is the most prevalent in people with HIV. Prolonged methamphetamine use can cause lasting damage to the heart, gut, and brain, as well as auditory hallucinations and paranoid thinking. However, relatively little is known about methamphetamine use and its genetic contributors. METHODS: Using genetic information from the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) cohort, we conducted a multi-ancestry genome-wide association study (GWAS) of methamphetamine use among people with HIV (n = 1,196 reported ever use, n = 4,750 reported never use). RESULTS: No single nucleotide polymorphism was statistically associated with methamphetamine use at the genome-wide level (p < 5 * 10-8) in our study. Further, we did not replicate previously suggested genetic variants from other studies (all p > 0.05 in our analysis). DISCUSSION: Our study suggests that there is no single strong genetic contributor to lifetime use of methamphetamine in people with HIV enrolled in CNICS. Larger studies with more refined outcome assessment are warranted to further understand the contribution of genetics to methamphetamine use and use disorder. Investigation into social and environmental contributors to methamphetamine use are similarly necessary.

Humans↗

PubMed2006

Estrogen, testosterone, and methamphetamine toxicity.

The gonadal steroid hormone, estrogen, can diminish the degree of striatal dopamine depletion resulting from methamphetamine. In this article, we describe the conditions of this estrogen neuroprotection as well as the potential for estrogen and testosterone to enhance methamphetamine-induced neurodegeneration of the nigrostriatal dopaminergic system. When administered prior to a neurotoxic regimen of methamphetamine, estrogen significantly decreases the amount of striatal dopamine depletion in intact or gonadectomized female, but not male, mice. This capacity for estrogen to function as a neuroprotectant can occur quite rapidly, at 30 min prior to methamphetamine administration, and with relatively low doses of estrogen (1 microg estradiol benzoate). Estrogen remains an effective neuroprotectant in neonatally gonadectomized female mice treated with testosterone, but not in female mice that were gonadectomized prior to puberty. Nor does estrogen demonstrate any beneficial effects when administered after methamphetamine. Recent data have indicated some conditions where gonadal steroids can increase the extent of striatal neurodegeneration in response to methamphetamine. Specifically, when some existing perturbation is present in the nigrostriatal dopaminergic system, treatment with estrogen enhances the extent of striatal dopamine depletion to methamphetamine. Similarly, increased striatal dopamine depletion to methamphetamine is observed in gonadectomized male mice treated with testosterone.

Animals↗

PubMed1987

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.

Animals↗

PubMed1986

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.

Animals↗

PubMed1984

Enhancement of behavioral effect and acute toxicity of methamphetamine by quinine 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. However, 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.

Animals↗

PubMed1993

[Effect of methamphetamine on the auditory system].

Four series of experiments were performed to evaluate the effects of methamphetamine on the auditory system of guinea pigs. Methamphetamine was administered to guinea pigs via intraperitoneal injection, and the time course of latencies of waves I, II, III, and IV, interpeak latencies of waves I-III, III-IV, and I-IV of the ABR, and the near-field potential of the inferior colliculus and cochlear nerve were measured. These physiological data were analyzed in comparison with the distribution of methamphetamine in the inferior colliculus and cochlea following its immunohistochemical staining, as well as the serum methamphetamine concentration. The following results were obtained; 1. The wave latencies and interpeak latencies of ABR decreased up to 120 minutes after the administration. 2. In the cochlear nerve recording, the amplitude of the response increased and the latency decreased up to 90 minutes after the administration. These changes in responses were, however more prominent in the inferior colliculus recording. 3. Immunohistochemical examination revealed that methamphetamine was present in the hair cells of the organ of Corti, spiral ligament, spiral ganglion cells and the inferior colliculus 30 minutes after the administration. 4. The serum concentration of methamphetamine rapidly reached its maximal level, and then dropped gradually, logarithmically, having become almost horizontal at a low level 6 hours later. These results suggest that methamphetamine does exert an effect on the peripheral auditory system, as well as on the central nervous system, which is generally regarded as the effector organ. It is assumed that the pharmacological effect of methamphetamine on the cochlea involves excitation of sensory cells, afferent nerve fibers and spiral ganglion cells.

Animals↗

PubMed1999

Methamphetamine-related deaths in San Francisco: demographic, pathologic, and toxicologic profiles.

A study was undertaken to develop demographic, toxicologic, and pathological profiles of methamphetamine-related deaths. Anatomic and toxicologic findings in 413 deaths where methamphetamine was detected were compared with findings in a control group of 114 drug-free trauma victims. The number of cases per year did not change significantly over the course of the study. Mean age was 36.8 years, but 11% were over the age of 50. Decedents were overwhelmingly male (85.2%) and Caucasian (75%). Blood concentrations of methamphetamine and amphetamine were indistinguishable in cases where methamphetamine was related to the cause of death (MR) and cases where it was not (non-MR) (2.08 vs. 1.78 mg/L, p = 0.65, and 0.217 vs. 0.19 mg/L, p = 0.82). Coronary artery disease, ranging from minimal to severe multivessel, was identified in 79 of the 413 drug users, but in only six of the 114 drug-free controls (p = 0.0004), and MR decedents had enlarged hearts compared with controls. There were also ten cases of subarachnoid and intracranial hemorrhage in the MR group. Abnormalities of the liver (34%) and lungs (24.7%) were frequent. In 65% of these cases, death was due to accidental methamphetamine toxicity. In the remaining cases, methamphetamine was an incidental finding. We conclude that, in our jurisdiction, neither the rate of detection nor the number of methamphetamine deaths has increased significantly in the past 13 years. Decedents are almost all Caucasian males, and many were approaching middle-age. Methamphetamine use is strongly associated with coronary artery disease and with subarachnoid hemorrhage.

Accidents↗

PubMed2001

Lobeline attenuates d-methamphetamine self-administration in rats.

alpha-Lobeline inhibits d-amphetamine-evoked dopamine release from striatal slices in vitro, appearing to reduce the cytosolic pool of dopamine available for reverse transport by the dopamine transporter. Based on this neurochemical mechanism of action, the present study determined if lobeline decreases d-methamphetamine self-administration. Rats were surgically implanted with jugular catheters and were trained to lever press on a fixed ratio 5 schedule for intravenous d-methamphetamine (0.05 mg/kg/infusion). To assess the specificity of the effect of lobeline, another group of rats was trained to lever press on a fixed ratio 5 schedule for sucrose reinforcement. Pretreatment of rats with lobeline (0.3-3.0 mg/kg, 15 min prior to the session) decreased responding for both d-methamphetamine and sucrose reinforcement. Following repeated lobeline (3.0 mg/kg) administration, tolerance developed to the decrease in responding for sucrose; however, the lobeline-induced decrease in responding for d-methamphetamine persisted. Furthermore, the lobeline-induced decrease in responding for d-methamphetamine was not surmounted by increasing the unit dose of d-methamphetamine. These results suggest that lobeline produces a nonspecific rate suppressant effect following acute administration, to which tolerance develops following repeated administration. Importantly, the results also suggest that repeated administration of lobeline specifically decreases responding for d-methamphetamine in a noncompetitive manner. Thus, lobeline may be an effective, novel pharmacotherapy for d-methamphetamine abuse.

Amphetamine-Related Disorders↗

PubMed2004

Involvement of some 5-HT receptors in methamphetamine-induced locomotor activity in mice.

Effects of some selective 5-HT antagonists on methamphetamine-induced locomotor activity were investigated in male mice in order to study whether this effect of methamphetamine is selectively or at least partially, induced through stimulation of a specific serotonin receptor subtype. Methamphetamine (1.5 mg/kg, IP) produced a significant increase in locomotor activity. Methamphetamine-induced hyperactivity by the above mentioned dose was significantly antagonized by NAN-190 ( 5-HT(1A) antagonist) at a dose of 4 mg/kg, IP, methiothepin (5-HT(1B/1D) antagonist) at a dose of 0.1mg/kg, IP or mianserin ( 5-HT(2C) antagonist) at a dose of 8 mg/kg, IP. On the other hand, methysergide ( 5-HT(2A/2B) antagonist) at a dose of 1mg/kg, IP or ondansetron ( 5-HT(3) antagonist) at a dose of 0.5mg/kg, IP potentiated the methamphetamine-induced hyperactivity. None of the above mentioned doses of 5-HT antagonists altered the spontaneous activity of mice when administered alone. The results of the present study indicate a possible role for serotonergic mechanisms, in addition to the catecholaminergic systems, in the locomotor stimulant activity of methamphetamine in mice. This role is possibly mediated through direct stimulation of some 5-HT receptor subtypes. Stimulation by methamphetamine of 5-HT(1A), 5-HT(1B/1D) and/or 5-HT(2C) receptor subtypes may result in hyperactivity, whereas stimulation by methamphetamine of 5-HT(2A/2B) and/or 5-HT(3) receptor subtypes may result in decreased activity.

Animals↗