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PubMed1994

Induction of neurotensin and c-fos mRNA in distinct subregions of rat neostriatum after acute methamphetamine: comparison with acute haloperidol effects.

Large increases of neurotensin (NT)-like immunoreactivity in the rat neostriatum have been reported previously after treatment with either dopamine D2 receptor antagonists (e.g., haloperidol) or potent indirect dopamine agonists (e.g., methamphetamine). Combined administration of these two opposite classes of drugs results in additive increases in striatal NT-like immunoreactivity suggesting that distinct mechanisms may underlie increases in NT content after haloperidol and methamphetamine. Our recent studies demonstrate that acute haloperidol treatment increases NT immunoreactivity in the striatum, at least in part, by enhancing the expression of the NT/neuromedin N (NT/N) gene in neurons confined to the dorsolateral sector of the striatum. Additionally, this induction of NT/N gene transcription in the dorsolateral striatum by haloperidol appears to involve participation of the immediate early gene, c-fos. The present study investigated alterations in NT/N and c-fos gene expression after acute methamphetamine (10 mg/kg s.c.) treatment and compared these changes to those observed after acute haloperidol (1 mg/kg i.p.) administration. Unlike haloperidol, methamphetamine increased NT/N mRNA expression in the periventricular dorsomedial quadrant of the striatum and induced c-fos mRNA primarily in the medial aspects of the central core of the neostriatum. These data suggest that Fos may not act as a primary transcription factor in methamphetamine-induced NT/N gene expression in the dorsomedial striatum. The results also indicate that additive increases in striatal NT-like immunoreactivity after simultaneous treatment with haloperidol and methamphetamine may be due to induction of NT/N gene expression in distinct neostriatal neuronal populations.

Animals↗

PubMed1996

Methamphetamine and driving impairment.

Following a review of the effects of methamphetamine on human performance, actual driving and behavior were evaluated in 28 cases in which drivers arrested or killed in traffic accidents had tested positive for methamphetamine. The circumstances surrounding the arrest or accident were examined, together with any observations by the arresting officer regarding behavioral irregularities. The investigators also made a determination of culpability. Most of the arrests resulted from accidents in which the driver was determined to be culpable. Typical driving behaviors included drifting out of the lane of travel, erratic driving, weaving, speeding, drifting off the road, and high speed collisions. Behavioral manifestations of methamphetamine use in arrestees included rapid or confused speech, rapid pulse, agitation, paranoia, dilated pupils, violet or aggressive attitude. Combined alcohol and methamphetamine use was uncommon, however use of marijuana was evident in about one third of the cases. In addition to impairing judgment and increasing risk taking, the effects of withdrawal from methamphetamine use including fatigue, hypersomnnolence, and depression are likely contributors to many of these accidents. A consideration of the literature and the cases discussed here, leads to the conclusion that methamphetamine at any concentration is likely to produce symptoms that are inconsistent with safe driving.

Adolescent↗

PubMed1996

Morphological and morphometric investigation of cardiac lesions after chronic administration of methamphetamine in rats.

The effects of chronic administration of methamphetamine on myocardium were morphologically and morphometrically studied in experimental models. Methamphetamine (1 mg/kg/day) was subcutaneously injected to five-week-old male Wistar Kyoto rats (WKY) for 8 weeks. Age- and sex-matched WKY served as controls. In light microscopy, scattered cytomyolysis, vacuolization, contraction bands and disarray of myofibers were prominent in methamphetamine-treated group; the electron microscopy showed degenerated mitochondria with disrupted cristae, myofibrillar hypercontraction and dissolution. Morphometric analysis was carried out using electron photographs and an image analyzer. The sizes of mitochondria and the number of mitochondria per unit area (100 microns2) in methamphetamine-treated group were significantly smaller than in the controls. No statistically significant difference was found regarding the percentage of myofibrillar area in cytoplasm between methamphetamine-treated and control groups. These findings show that chronic administration of methamphetamine can cause serious cardiac lesions and decrease in mitochondrial function.

Animals↗

PubMed1997

[Histopathological study on acute poisoning of methamphetamine, morphine or cocaine].

Methamphetamine, morphine or cocaine was injected intraperitoneally into Wistar rats (male, 6 weeks old) at a dose of 50 mg/kg, 125 mg/kg, or 50 mg/kg body weight, respectively. These doses of drugs were determined to ensure that the rats would show signs of drug intoxication and survive for a day. Over the period from 5 min to 18 hr after injection, concentrations of the drugs and metabolites in blood were analyzed by the GC/MS method, and the histopathological changes of the heart, lungs, liver and kidneys were examined by light microscopy. The time of maximum drug concentration in the blood after injection was 5 min in the methamphetamine-treated group, 1 hr (total morphine) in the morphine group and 5 min in the cocaine group. These blood concentrations decreased with time. In the liver at 2.5 hr after injection of methamphetamine, centrolobular vacuolation and diffuse eosinophilic changes of hepatocytes appeared. At 6 hr this damage spread to the midzone of the liver and partial necrosis of the centrolobe was found. At 18 hr the liver damage became worse and necrosis was also found in the midzone of the liver. In the heart, from 2.5 hr, eosinophilic changes of the myocardium were observed diffusely. Furthermore, at 18 hr, partial inflammatory cell infiltration and contraction bands were observed. The degree of histopathological damage did not coincide with the time of maximum drug concentration. In the morphine group, centrolobular and midzonal vacuolation, diffuse fatty degeneration and eosinophilic changes were observed in the liver from 2.5 hr to 18 hr after the administration. No necrosis was found, perhaps because the rats did not suffer the hyperthermia observed in the methamphetamine group. The degree of histopathological damage became more serious with time, as it did in the methamphetamine group. In the cocaine group, no histopathological changes were observed, probably because the doses of cocaine were too small to cause histopathological damage, and because cocaine is more rapidly metabolized than methamphetamine or morphine. These results suggest that in histopathological investigations necessitated by drug intoxication, measuring drug concentrations in the blood might be useful in determining the causes of histopathological changes more clearly.

Animals↗

PubMed1997

Potential new insights into the molecular mechanisms of methamphetamine-induced neurodegeneration.

In the event that methamphetamine evokes HO. formation within serotonergic axon terminals, the resultant oxidation of 5-HT would be expected to generate not only 5,6-DHT but also T-4,5-D, 7-S-Glu-T-4,5-D, 6, 8, and 7,7'-D (figure 1), at least three of which (T-4,5-D, 7-S-Glu-T-4,5-D, and 6) are lethal in mouse brain. Furthermore, several intermediates/products formed in the in vitro oxidation of 5-HT by HO. are readily autoxidized (4,5-DHT, 5,6-DHT, 5, 7, and 9) or redox cycled (T-4,5-D, 6, 8, 7,7'-D, 7-S-Glu-T-4,5-D) in reactions that would be expected to yield O2-. and/or H2O2 as byproducts. These byproducts, in the presence of trace levels of transition metal ion catalysts, would be readily converted into HO. (Walling 1975; Halliwell and Gutteridge 1984). Together these putative aberrant oxidative metabolites of 5-HT and HO.-forming reactions might contribute to the degeneration of serotonergic nerve terminals. Similarly, the methamphetamine-induced intraneuronal formation of HO. in dopaminergic terminals might be expected to generate not only 6-OHDA (and 2-OHDA and 5-OHDA, figure 3) but also 5,-S-CyS-DA and 5-S-Glu-DA, precursors of DHBT 17 and other more complex dihydrobenzothiazines (figure 4). DHBTs 17 to 19 are lethal in mouse brain, although at this time the biochemical/chemical mechanisms underlying this toxicity and specific neuronal systems affected are unknown. However, 5-S-CyS-DA and 17 to 19 are much more easily oxidized than DA, and the latter DHBTs appear to be capable of redox cycling reactions (Zhang and Dryhurst 1994). Thus, the HO.-mediated oxidation of DA in dopaminergic nerve terminals induced by methamphetamine might be expected to generate aberrant oxidative metabolites that (as a result of autoxidation and redox cycling reactions) potentiate formation of O2-. and/or H2O2, and then HO. and neuronal damage. A number of lines of evidence, discussed previously, suggest that aberrant metabolite(s) of DA (other than or in addition to 6-OHDA) might contribute to the methamphetamine-induced degeneration of not only dopaminergic terminals but also serotonergic terminals. Similarly, aberrant metabolite(s) of 5-HT (other than or in addition to 5,6-DHT) might be involved in the degeneration of serotonergic and dopaminergic terminals and a subpopulation of cell bodies in the somatosensory cortex. Experimental evidence indicates that some of the neurodegenerative effects evoked by methamphetamine are mediated by NMDA and GABA receptors. Thus, it will be of considerable interest to investigate the neurotoxicity of putative aberrant oxidative metabolites of 5-HT (figures 1 and 2) and DA (figures 4 and 5) towards serotonergic, dopaminergic, and other neuronal systems and their interactions with NMDA, GABA, and other brain receptors. A central question relates to mechanisms by which methamphetamine might evoke the intraneuronal formation of oxygen radicals that appear to play important roles in the overall neurodegenerative processes evoked by this drug (DeVito and Wagner 1989; Cadet et al. 1994). Once putative oxidative metabolites of 5-HT such as T-4,5-D, 7-S-Glu-T-4,5-D, 5,6-DHT, 6, 8, and 7,7'-D (figure 1) are formed intraneuronally, autoxidation/redox cycling reactions should, in principle, be capable of generating O2-. and/or H2O2, the precursors of HO.. Similarly, intraneuronal formation of 6-OHDA, 5-S-CyS-DA, and DHBTs 17 to 19 and 22 would also be expected to potentiate elevated fluxes of O2-., H2O2, and HO. as a result of the facile autoxidation/redox cycling reactions of these putative aberrant metabolites. The presence of very low concentrations of 5-S-CyS-DA in DA-rich regions of human and other mammalian brains suggest that autoxidation (Rosengren et al. 1985; Fornstedt et al. 1986, 1989, 1990) or perhaps some other form of DA oxidation is a normal reaction in vivo. Furthermore, available evidence suggests that it is cytoplasmic DA that is oxidized to give 5-S-CyS-DA (Fornstedt et al. 1989; Fornstedt and

Animals↗

PubMed1999

Methamphetamine as a risk factor for acute aortic dissection.

Acute aortic dissections are catastrophic vascular events that have a high rate of mortality. Aortic dissections have been associated with a variety of factors, particularly hypertension. We reviewed 84 medical examiner autopsies on individuals dying from acute aortic dissections with particular emphasis on the role of drugs. Previous case reports have associated aortic dissections with both cocaine and methamphetamine intoxication. We found that seven of the 35 cases tested for drugs of abuse were positive for methamphetamine. Our study had no cases of solely cocaine-related dissection, although one of the cases was positive for both methamphetamine and the cocaine metabolite benzoylecgonine. No significant association was found with any other drugs. As with other studies, we found the most common risk factor to be hypertension. Surprisingly, methamphetamine use was the second most common risk factor. The association between methamphetamine use and aortic dissection is most likely due to its hypertensive effect. Although methamphetamine appears to pose a greater risk than cocaine, both drugs should be considered as possible factors in all aortic dissections.

Acute Disease↗

PubMed1996

Effects of H(1)-antagonists on discriminative stimulus effects of cocaine and methamphetamine in rats.

The effects of H(1)-antagonists, such as tripelennamine, chlorpheniramine and pyrilamine, on the discriminative stimulus effects of cocaine and methamphetamine in rats were examined. Rats were trained to discriminate between cocaine (10mg/kg, i.p.) or methamphetamine (1.0mg/kg, i.p.) and saline, with responses maintained under a fixed-ratio 10 (FR10) schedule of food delivery. In generalization tests, tripelennamine generalized to the discriminative stimulus effects of cocaine and methamphetamine, while chlorpheniramine only generalized to cocaine. These generalizations of tripelennamine and chlorpheniramine were attenuated by the dopamine receptor antagonist haloperidol. Furthermore, tripelennamine and chlorpheniramine, but not pyrilamine, potentiated the discriminative stimulus effects of cocaine and methamphetamine. These results suggest that some H(1)-antagonists possess cocaine- and/or methamphetamine-like discriminative stimulus effects which may be mediated by the dopaminergic system, and as a result the discriminative stimulus effects of cocaine and methamphetamine were potentiated by these H(1)-antagonists.

Journal Article↗

PubMed2026

Care Navigation for Methamphetamine Use Disorder: A Randomized Clinical Trial.

IMPORTANCE: Stimulant-involved deaths continue to increase in the US, and methamphetamine use remains a weighty public health concern. Treating methamphetamine use disorders is complicated. Contingency management has demonstrated the best effectiveness but is not widely implemented. OBJECTIVE: To examine the effectiveness of dedicated care navigation in linking patients to treatment. DESIGN, SETTING, AND PARTICIPANTS: This prospective randomized clinical trial was conducted at an integrated safety-net health system in Denver, Colorado, between April 10, 2023, and December 31, 2024. Eligible participants were 18 years or older who had a methamphetamine-related encounter in an acute care setting; those with involuntary treatment holds, substance treatment in past 90 days or actively seeking treatment, and inability to provide consent were excluded. Participants completed baseline, 30-day, and 90-day study visits. INTERVENTION: Dedicated care navigation, incorporating contingency management principles, with a focus on addressing health-related social needs. MAIN OUTCOMES AND MEASURES: Linkage to treatment within 30 and 90 days of enrollment defined as a composite measure of at least 1 of the following: electronic health record data indicating a visit at the health system's substance treatment clinic, a behavioral health encounter at an outpatient clinic, temporary residential treatment, or self-reported treatment on the 30- and/or 90-day follow-up survey. RESULTS: Of 192 participants enrolled in the Beginning Early and Assertive Treatment for Methamphetamine Use trial, 156 (81.3%) were male, and the median age was 39 (IQR, 31-47) years. Most participants were unstably housed (163 [84.9%]), not currently employed (158 [82.3%]), and without regular access to a working phone (94 [49.0%]). Of the 96 participants randomized to the intervention, 60 (62.5%) engaged in 2 or more navigation sessions, 45 (46.9%) completed the 30-day study visit, and 47 (49.0%) completed the 90-day study visit compared with 44 (46.3%) and 37 (38.5%), respectively, of the 96 randomized to the control arm. No statistically significant differences in treatment linkage were observed at 30 days (24 participants [25.0%] in both arms; risk ratio, 1.00 [95% CI, 0.61-1.63]) or 90 days post enrollment, (32 [33.3%] in intervention vs 24 [25.0%] in control arms; risk ratio, 1.33 [95% CI, 0.85-2.09]). CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, integrating principles of contingency management into the intervention may have increased engagement with a dedicated care navigator but did not increase likelihood of linkage to treatment for methamphetamine use disorder. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06033365.

Humans↗

PubMed1983

Determination of methamphetamine in hair after single and repeated administration to rat.

Methamphetamine in hair after p.o. administration to rat was identified and determined by mass fragmentography (MF). Rat hair was washed with HCl/methnanol, methanol and water. The hair was crushed in 0.6 M HCl, suspension was alkalized with Na2CO3, and extracted with chloroform/isopropanol. The extract obtained was purified by column chromatography on aluminium oxide. Concentrated eluate was trifluoroacetylated, and methamphetamine was identified and determined by MF. More than 20 pg of methamphetamine was detectable and less than 1 ng of that was determined by MF. Methamphetamine in hair collected from rat after p.o. administration of 20 mg/kg of the drug was detected and determined up to 8 days after. From hair of rat after 5-days or 14-days repeated administration of 20 mg/kg/day, methamphetamine was detected 25 or 45 days after the last administration, respectively.

Animals↗

PubMed1979

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.

Animals↗

PubMed1978

Methamphetamine and diphenhydramine effects on the rate of cognitive processing.

Three cognitive tasks in which performance depends primarily on the rate of cognitive processing were given to 24 male subjects before and after oral doses of methamphetamine (10 mg), diphenhydramine hydrochloride (100 mg), and placebo. Each subject was tested on Monday, Wednesday, and Friday of one week with drug orders balanced across subjects. Compared with placebo and diphenhydramine, methamphetamine increased the rate at which a visual display was scanned for a target stimulus. Methamphetamine affected neither a time-production task nor a divided attention task that required the subject to perform two cognitive tasks in a limited amount of time. This suggests that methamphetamine can increase cognitive processing speed on tasks involving familiar cognitive operations but that an increase is not likely in tasks involving more complicated decision processes. Compared with placebo and methamphetamine, diphenhydramine caused subjects no experience geophysical time as passing more slowly, but the drug had no significant effects on the visual search or divided-attention tasks. This suggests that time perception is more likely to be altered by diphenhydramine than is performance on tasks requiring short periods of rapid cognitive processing.

Adolescent↗

PubMed1986

Effect of chronic administration of methamphetamine on the responsiveness of substantia nigra zona reticulata neurons to GABA or a GABA agonist in rats.

The effects of chronic administration of methamphetamine on the responsiveness of neurons of the substantia nigra zona reticulata (SNR) to gamma-aminobutyric acid (GABA) or to a GABA receptor agonist were examined. Neuronal activity was recorded from the SNR of rats that had been pretreated twice daily, for 6 consecutive days, with saline or with 5 mg/kg methamphetamine. Intravenous administration of the GABA receptor agonist, muscimol, caused a dose-dependent decrease in the unit activity of the SNR neurons and the SNR neurons became less sensitive to the depressant effects of the drug after chronic treatment with methamphetamine. Iontophoretic application, with increasing currents, of GABA produced a progressive inhibition of unit activity in control animals, an effect that was significantly reduced in rats pretreated with methamphetamine. These results support the hypothesis that long-term administration of methamphetamine increases the activity of the striatonigral GABA system and thereby reduces the sensitivity of postsynaptic GABA receptors in the SNR.

Animals↗

PubMed1992

A comparison of the effects of sibutramine hydrochloride, bupropion and methamphetamine on dopaminergic function: evidence that dopamine is not a pharmacological target for sibutramine.

Sibutramine hydrochloride, a novel monoamine reuptake inhibitor antidepressant, has been studied to determine whether it alters dopaminergic function in the brain. Its effects have been compared with bupropion, a dopamine reuptake inhibitor, and methamphetamine, a dopamine reuptake inhibitor and releasing agent. Sibutramine (0.1-3 mg/kg PO) and methamphetamine (0.3-30 mg/kg PO) both prevented reserpine (0.75 mg/kg IV) ptosis in rats with ED50 values of 0.6 mg/kg and 4.2 mg/kg, respectively. Bupropion (10-100 mg/kg PO) was ineffective against reserpine ptosis. The efflux of [3H]-dopamine from preloaded rat striatal slices was not altered by 10(-7)-10(-5) M concentrations of sibutramine, BTS 54,354, BTS 54,505 (secondary and primary amine metabolites, respectively) or bupropion. In contrast, methamphetamine (10(-8)-10(-4) M) caused a significant concentration-dependent increase in [3H]-dopamine release. Sibutramine (3 mg/kg IP or 6 mg/kg PO) and bupropion (10 mg/kg IP or 30 mg/kg PO) did not alter 3-methoxytyramine (3-MT) levels in rat striatum. Striatal 3-MT concentrations were, however, dose-dependently increased by methamphetamine (0.3-10 mg/kg IP or 0.42-4.2 mg/kg PO). Sibutramine (6 mg/kg PO) did not induce circling in rats with unilateral 6-hydroxydopamine lesions of the nigrostriatal dopaminergic neuronal tract. Bupropion (10-100 mg/kg PO) did not induce circling at the lowest dose, but caused increasing ipsilateral rotation at higher doses. Methamphetamine (0.42 or 4.2 mg/kg PO) induced ipsilateral circling with marked effects at the higher dose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1995

Effects of pargyline and pyrogallol on the methamphetamine-induced dopamine depletion.

The formation of 6-hydroxydopamine (6-OHDA) from dopamine (DA) was investigated in the striatum of male Sprague-Dawley rats following a single administration of methamphetamine hydrochloride (100 mg/kg, sc). Rats were sacrificed 30, 60, and 90 min, and 1 wk after injection, and striatal 6-OHDA, DA, and 3,4-dihydroxyphenylacetic acid (DOPAC) were measured by HPLC with electrochemical detection. Methamphetamine decreased striatal DA and DOPAC levels (to 65 and 50% at 90 min, respectively) in the time-course study and also resulted in a long-lasting dopamine depletion (34%) 1 wk after its administration. However, endogenous 6-OHDA formation proved difficult to detect after administration of the methamphetamine alone. Pretreatment with the monoamine oxidase (MAO) inhibitor pargyline (100 mg/kg, ip) and the catechol-O-methyltransferase (COMT) inhibitor pyrogallol (25 mg/kg, ip) resulted in the HPLC detection of a 6-OHDA-like substance 30 min after methamphetamine administration when the oxidizing potential was set at 0.5 V, but not when it was set at 0.2 V. Moreover, pargyline (25 mg/kg, ip) alone or in combination with pyrogallol exacerbated the long-lasting dopamine depletion induced by methamphetamine (50 mg/kg, sc). These results indicate that simultaneous inhibition of MAO and COMT provides a cellular environment that encourages the autoxidation of dopamine to a 6-OHDA-like substance.

3,4-Dihydroxyphenylacetic Acid↗

PubMed2000

Adult treatment with methamphetamine transiently decreases dentate granule cell proliferation in the gerbil hippocampus.

The objective of the present study was to examine whether acute treatment with the recreational drug methamphetamine influences adult granule cell proliferation in the dentate gyrus of the hippocampus. For that purpose, at the age of postnatal day 90 adult male gerbils (Meriones unguiculatus) received a single dose of either methamphetamine (25 mg/kg; i.p.) or saline. Proliferation of granule cells was identified by in-vivo labeling with 5-bromo-2'-desoxyuridine (BrdU) which was applied either simultaneously with methamphetamine or 36 h after administration of the drug. BrdU-labeled granule cell nuclei were identified in consecutive horizontal slices along the mid-septotemporal axis of the hippocampus and light-microscopically quantified 7 days after the BrdU-labeling. It was found that in both saline- and methamphetamine-treated animals there was a highly significant spatial septotemporal gradient in granule cell proliferation with numbers of BrdU-labeled cells gradually declining from the septal towards the temporal pole. The acute treatment with methamphetamine suppressed granule cell proliferation by about 28% and the septotemporal gradient of mitotic activity became significantly attenuated. It was further found that 36 h after the drug challenge granule cell proliferation rates had been restored almost to the control values along the whole septotemporal axis of the hippocampus. The present results are discussed with regard to (1) pharmacological regulation of neurogenesis in the hippocampus and (2) probable clues they may provide for both understanding the biological correlates of psychotic disorders and evolution of future concepts in neuropharmacological intervention.

Age Factors↗

PubMed2001

Opioid peptides alleviated while naloxone potentiated methamphetamine-induced striatal dopamine depletion in mice.

Delta opioid peptide [D-Ala2, D-Leu5] enkephalin (DADLE) can partially reverse long-term loss of striatal dopamine transporters induced by multiple doses of methamphetamine via an unknown mechanism. This study was designed to examine the modulating effects of three opioid ligands, DADLE, Leucine enkephalin (L-enk), and naloxone, on the long-lasting dopamine depletion produced by 4 cumulative doses of methamphetamine. Both DADLE (at a dose of 18 mg/kg) and L-enk (100 microg/kg x 2) effectively attenuated methamphetamine-induced dopamine depletion in the striatum while their protective effects were not blocked by coadministration of naloxone. In contrast, naloxone (10 mg/kg x 2) alone potentiated the long-lasting dopamine depletion produced by methamphetamine. Moreover, none of the treatments with DADLE (18 mg/kg), L-enk (100 microg/kg), or naloxone (10 mg/kg) alone affected body temperature. These results suggest that the opioid ligands may, directly or indirectly, modulate this methamphetamine-induced dopamine neurotoxicity in the nigrostriatal system via a temperature-independent mechanism.

Animals↗

PubMed2006

Management of methamphetamine abuse and dependence.

Preliminary implications for evidence-based treatments and future practice may be drawn from new research findings that inspire a fresh view of methamphetamine dependence and associated medical consequences. Current user populations include increasingly impacted subgroups (ie, youths, women, men who have sex with men, and rural residents); complex consequences of methamphetamine abuse among these subgroups require additional efforts involving contextual understanding of characteristics and needs to develop effective treatments. The neurobiological data on cellular activity of methamphetamine taken with findings from neuroimaging studies indicate potential targets for pharmacologic interventions. In early trials, several candidate medications--bupropion, modafinil, and, to a lesser extent, baclofen--have shown promise in treating aspects of methamphetamine dependence, including aiding memory function necessary to more effectively participate in and benefit from behavioral therapies. Clinicians and researchers must interact to efficiently address the problems of methamphetamine dependence, a major drug problem in the United States and the world.

Baclofen↗

PubMed1983

Alpha-methyltyrosine attenuates and reserpine increases methamphetamine-induced neuronal changes.

The repeated administration of methamphetamine to rats has been shown to cause a long-lasting depletion of dopamine in various brain regions. In the first study, the effects of pretreatment with alphamethyltyrosine (AMT) or reserpine on the long-lasting methamphetamine-induced dopamine depletion were examined. In the second study, the effects of AMT and reserpine on central dopamine levels were measured in rats previously treated with methamphetamine. Pretreatment with AMT attenuated the long-lasting dopamine depletion induced by methamphetamine, whereas, pretreatment with reserpine increased the depletion. The acute effects of AMT and reserpine on brain dopamine were not altered when administered two weeks after the last methamphetamine injection.

Animals↗