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PubMed2004

Conditioned place preference and locomotor sensitization after repeated administration of cocaine or methamphetamine in rats treated with epidermal growth factor during the neonatal period.

Epidermal growth factor (EGF) and its structurally related proteins are involved in the developmental regulation of various brain neurons, including midbrain dopaminergic neurons. We recently reported EGF and EGF-receptor abnormalities in both the brain tissues and blood of schizophrenic patients. Administration of EGF to neonatal rats transiently increases tyrosine hydroxylase expression and subsequently results in behavioral abnormalities in prepulse inhibition of acoustic startle, locomotor activity, and social interaction after development. The enhanced locomotor and stereotypic responses of the neonatally EGF-treated rats are considered to be an animal model for positive schizophrenia symptoms. In the present study, we investigated psychostimulant sensitivity of neonatally EGF-treated rats. At the adult stage, EGF-treated rats were challenged with cocaine (15 mg/kg) or methamphetamine (1 mg/kg), and conditioned place preference and locomotor activity were examined. The rats that received EGF during the neonatal period had significantly higher conditioned place preference for where cocaine or methamphetamine was administered than controls. The neonatal EGF treatment enhanced behavioral response to methamphetamine and behavioral sensitization to cocaine at the adult stage. Drug-naive controls gradually increased locomotor responses to cocaine during their daily injections, whereas EGF-treated rats exhibited a larger increase in cocaine responses. These results indicate that overactivation of the EGF receptors (ErbB1) during the neonatal period influences future sensitivity to psychostimulants. Our findings indicate a potential link between EGF-receptor activation and drug addiction.

Animals↗

PubMed1980

The emotional communication based on methamphetamine mortality as the index in olfactory bulbectomized mice.

The emotional transmission was studied in olfactory bulbectomized mice by the communication box method using methamphetamine toxicity (mortality) as the index. Intraperitoneal administration of methamphetamine 15 mg/kg in the sender, responder and control groups of olfactory bulbectomized mice resulted in a marked rise of mortality in the sender and responder groups, compared to the control group. In the sham-operated mice, on the other hand, the mortality markedly rose in the sender group, but the mortality of the responder group was lower than that of the sender group, and was higher than that of the control group. As the result of studies on the emotional transmission using methamphetamine toxicity, the emotional reaction in the sender group appears to be transmitted to the responder group in olfactory bulbectomized animals.

Animal Communication↗

PubMed1976

[Effects of methamphetamine and a reserpine-like drug on norepinephrine and dopamine metabolism in the rat brain].

Simple and sensitive methods for the separation and determination of catecholamines and their metabolites by thinlayer microcrystalline cellulose chromatography have been developed and applied to the analysis of norepinephrine (NE) and dopamine (DA) metabolism in the brain of Wistar rats given 12C-NE or 14C-DA intraventricularly. 14C-DA in the whole brain declined more rapidly than did 14C-NE. The percentage of unchanged 14C-NE in total radioactivity in the brain of rats administered 14C-NI was high, while on the other hand, the percentage of unchanged 14C-DA in cases of 14C-DA was low. In the metabolism of 14C-DA, the deaminated and O-methylated deaminated metabolites showed transient and delayed temporary rises, respectively. Drugs which affect the metabolism of catecholamines were also examined. Methamphetamine reduced NE, deaminated and O-methylated deaminated metabolites, and markedly elevated normetanephrine in the brain of rats given 14C-NE. Regarding the metabolism of DA, methamphetamine increased 3-methoxytyramine and homovanillic acid and reduced deaminated metabolites, but had no effect on DA and NE. On the other hand, a reserpine-like drug (Ro4-1284) reduced NE and increased deaminated and O-methylated deaminated metabolites in the metabolism of NE, and reduced to a great extent DA and NE and increased homovanillic acid in the metabolism of DA. From these results, it is concluded that the effect of methamphetamine was more evident in NE metabolism than DA, while the effect of Ro4-1284 was more evident in DA metabolism than NE.

2H-Benzo(a)quinolizin-2-ol, 2-Ethyl-1,3,4,6,7,11b-↗

PubMed1984

The difference in the site of actions of tricyclic antidepressants and methamphetamine on the duration of the immobility in the behavioral despair test.

A single administration of tricyclic antidepressants reduced the duration of the immobility in the behavioral despair test. The escape-directed behavior of tricyclic antidepressant-treated rats was observed in a cylinder partially filled with water. In contrast, although methamphetamine also reduced the duration of the immobility, an increase in the general motor activity was shown in methamphetamine-treated rats. Tricyclic antidepressants injected into the medial amygdaloid nucleus, not into the nucleus accumbens, suppressed the duration of the immobility. Methamphetamine completely suppressed the duration of the immobility not only when injected into the medial amygdaloid nucleus, but also when injected into the nucleus accumbens. The present results suggest that in the rat behavioral despair test, the medial amygdaloid nucleus may play an important role in the selective reductive effect on the duration of the immobility.

Amygdala↗

PubMed1985

Effects of methamphetamine on dopamine cells in the substantia nigra pars compacta and the ventral tegmental area.

The ability of methamphetamine to inhibit the firing rate of dopamine cells in the substantia nigra pars compacta (SNC) and the ventral tegmental area (VTA) was studied. Methamphetamine reduced the firing rates of the dopamine cells in a dose-dependent manner in the SNC and the VTA. The doses of methamphetamine required to produce a 50% inhibition of firing rate in the SNC and the VTA were 0.37 mg/kg and 0.28 mg/kg, respectively.

Animals↗

PubMed1986

Effect of caerulein with haloperidol on monoamine contents in rat brain regions treated with methamphetamine.

To elucidate the mechanism of the antagonistic effect of caerulein on amphetamine-induced hyperactivity, monoamine contents in rat brain regions were measured by HPLC. With a combination of caerulein and haloperidol, dopamine contents in methamphetamine treated-rats were significantly decreased in the striatum. Noradrenaline contents were significantly decreased in the haloperidol-methamphetamine group, but caerulein restored it to the normal levels. Serotonin contents did not change in any of the groups tested. These results may indicate that caerulein acts as a neuromodulator in rat brain and causes suppression of hyperactivity induced by methamphetamine.

Animals↗

PubMed1991

Differential antagonism of the stimulant effects of MK-801 and methamphetamine by ceruletide: evaluation by discrete shuttle avoidance response in mice.

A noncompetitive NMDA antagonist MK-801 (0.03-0.3 mg/kg, i.p.) increased the response rate of mice trained under the discrete shuttle avoidance situation to a degree similar to the increase by methamphetamine (0.1-1 mg/kg, i.p.). The cholecystokinin-like decapeptide ceruletide significantly reduced the response-increasing effect of MK-801 (0.1 mg/kg) at 0.001 micrograms/kg; however, only 10 micrograms/kg of ceruletide, which per se inhibited the response, attenuated that of methamphetamine (0.3 mg/kg). The coadministration of MK-801 (0.1 mg/kg) and methamphetamine (0.3 mg/kg) produced no potentiation of the effect, and almost the same effect was maintained even after the additional administration of ceruletide (0.1 microgram/kg).

Animals↗

PubMed1993

SCH 23390 equivalently, but YM-09151-2 differentially reduces the stimulant effects of methamphetamine, MK-801 and ketamine: assessment by discrete shuttle avoidance in mice.

The inhibitory actions of the selective dopamine D1-and D2-antagonists SCH 23390 and YM-09151-2, respectively, on the mouse's discrete shuttle avoidance were almost equipotent at doses ranging from 0.01-0.1 mg/kg. SCH 23390 reduced the stimulant action of methamphetamine (0.5 mg/kg), MK-801 (0.1 mg/kg) and ketamine (10 mg/kg) with a similar potency. YM-09151-2 also antagonized the actions of these drugs, with the following order of effectiveness: ketamine > MK-801 > methamphetamine. The present results indicate that methamphetamine, MK-801 and ketamine have different characteristics of CNS stimulant action through dopamine D2-receptors.

Animals↗

PubMed2002

Patient characteristics, HIV serostatus, and risk behaviors among gay and bisexual males seeking treatment for methamphetamine abuse and dependence in Los Angeles.

Methamphetamine, a drug used at alarming rates among gay/bisexual males in the West, is often combined with sexual activities, thereby increasing HIV-related risks in an already high-risk group. Findings from 68 gay/bisexual men seeking treatment for methamphetamine dependence in Hollywood, California were analyzed to predict HIV serostatus based on demographic, drug use, or sexual behavior variables. Results showed that more HIV-infected participants than non-infected men reported medical problems (97.6% versus 46.2%; X2 = 24.7, df = 1, p < .0001), histories of genital gonorrhea (59.5% versus 26.9%; X2 = 6.9, df = 1, p < .01), use of injection methods (45.2% versus 19.2%; X2 = 4.8, df = 1, p < .03), and more sexual partners with unprotected receptive anal intercourse in the 30 days prior to intake (5.9 versus 0.7; separate t = 3.5, df = 43.7, p < .001). More non-infected participants (19.2%) reported suicidal thoughts than HIV-infected men (0%; X2 = 4.8, df = 1, p < .03). Discriminant function analysis correctly classified 74.6% of cases into serostatus groupings based on presence of suicidal thoughts, history of gonorrhea, number of sexual partners with unprotected receptive anal intercourse and prior methamphetamine treatment. Findings provide information that may prove helpful in tailoring culturally relevant treatment and prevention messages.

AIDS Serodiagnosis↗

PubMed2005

HIV-associated medical, behavioral, and psychiatric characteristics of treatment-seeking, methamphetamine-dependent men who have sex with men.

This paper examines medical and psychiatric symptoms and disorders associated with reported HIV serostatus among methamphetamine-dependent, treatment-seeking men who have sex with men (MSM) in Los Angeles. Baseline data from a NIDA-funded, randomized clinical trial of behavioral drug abuse therapies included medical examinations and behavioral interviews of the 162 randomized participants. Variables identified as significantly associated with HIV infection were entered into a multivariate, hierarchical logistic regression analysis to optimally predict HIV serostatus. The disturbingly high 61% of the sample with reported HIV-seropositive status represents 3-4 times the prevalence for all MSM in Los Angeles County. HIV infection status strongly associated with prior treatment for methamphetamine dependence; unprotected receptive anal intercourse; history of sexually transmitted infections; and health insurance status. Findings demonstrate the powerful connection between methamphetamine dependence and HIV infection, and strongly suggest a need for development of interventions that function as both substance abuse treatment and HIV prevention for this population.

Adult↗

PubMed2005

A comparison of methamphetamine-dependent inpatients childhood attention deficit hyperactivity disorder symptomatology.

Methamphetamine-dependent inpatients (N = 51) were screened for childhood attention deficit hyperactivity disorder (ADHD) using the Wender Utah Rating Scale upon admission to 30-day inpatient treatment. Baseline assessments included neuropsychological tests of executive function, memory, information processing, verbal fluency, attention, motor skills, and the Brief Symptom Inventory (BSI), a measure of psychiatric symptomatology. The thirty-six participants (70.6%) screening positive for ADHD reported significantly more frequent methamphetamine use prior to baseline. Baseline cognitive functioning was similar between groups, but the presumptive ADHD participants exhibited significantly worse psychiatric symptomatology. At three-week follow- up, 41 participants (80.4%) repeated the neuropsychological battery and BSI. All 10 non-completers screened positive for ADHD. The entire sample improved with abstinence in most neuropsychological domains except memory. The presumptive ADHD group failed to improve on tests of attention. All participants demonstrated significant reductions in psychiatric symptoms with abstinence. Methamphetamine-dependent individuals with ADHD symptoms are common and pose a significant treatment challenge.

Adult↗

PubMed2006

Clinical effects and management of methamphetamine abuse.

Methamphetamine is a highly potent and addictive drug that is abused in the United States and around the world. The drug is inexpensive and easily manufactured from simple chemicals such as pseudoephedrine. These features, coupled with its long half-life and highly addictive nature, contribute to the increasing problem of illicit methamphetamine use. Abuse of this agent has both acute and chronic serious health consequences. Policy makers and public health officials must continue to develop programs that educate the public and limit the abuse associated with methamphetamine.

Amphetamine-Related Disorders↗

PubMed1994

Human d-amphetamine drug discrimination: methamphetamine and hydromorphone.

Standard measures of subjective and discriminative effects of drugs were compared in 5 human volunteers. Subjects responded on a second-order color-tracking procedure, where 30 mg of d-amphetamine served as a discriminative stimulus for one response and its absence as the discriminative stimulus for another response. Self-reported subjective effects were assessed concurrently using the single-dose questionnaire, subscales of the Addiction Research Center Inventory, and several analogue rating scales. On different days following discrimination acquisition, varying doses of d-amphetamine, methamphetamine, and hydromorphone were administered. In these test sessions, either response was reinforced. Methamphetamine and d-amphetamine occasioned dose-related increases in d-amphetamine appropriate responding; hydromorphone did not. Methamphetamine and d-amphetamine occasioned dose-related increases in reports of the drug received being most like "speed"; hydromorphone occasioned dose-related increases in reports of the drug received being most like "dope." All three drugs occasioned dose-related increases in reports of drug liking, and increases in the morphine-benzedrine group, amphetamine, and benzedrine group scales of the Addiction Research Center Inventory. This experiment demonstrated that although explicit discriminative control of behavior by a drug may covary with drug identification, it does not necessarily covary with other self-reported subjective effects. Thus, the complementary nature of the data provided by drug discrimination and standard subjective-effects measures provides quantitative and qualitative data useful in studying both relatively novel compounds and the behavioral biology of psychoactive drugs in general.

Adult↗

PubMed1982

Sedative action of cholecystokinin octapeptide on behavioral excitation by thyrotropin releasing hormone and methamphetamine in the rat.

Intracerebroventricular (i.c.v.) injection of C-terminal octapeptide of cholecystokinin (CCK-8) in rats prolonged pentobarbital- and ethanol-induced sleeping time, but non-sulfated CCD-8 (CCK-8-NS) had no effect and caerulein showed a tendency to prolong the pentobarbital narcosis. On the other hand, i.c.v. injection of thyrotropin releasing hormone (TRH) shortened the sleeping time and the effect of CCK-8 was apparently antagonized by combined administration of TRH. Spontaneous locomotor activity in the late morning and early afternoon was not affected by CCK-8, but it increased following i.c.v. injection of CCK-8-NS. Hyperactivity produced by TRH and methamphetamine was suppressed by i.c.v. injection of CCK-8, while CCK-8-NS showed a tendency to enhance the methamphetamine-induced hyperactivity and caerulein had no effect. These results indicate that CCK-8 has a sedative action and antagonizes the behavioral excitation caused by TRH and methamphetamine, but that the effects of CCK-8-NS and caerulein were rather the opposite of those of CCK-8. In an additional experiment the TRH-induced body shaking response was not affected by combined administration of CCK-8.

Animals↗

PubMed1982

Distribution and excretion of methamphetamine and its metabolites in rats. I. Time-course of concentrations in blood and bile after oral administration.

1. Concentration time-courses of methamphetamine and its metabolites in the blood after oral administration of [3H]methamphetamine to rats showed two distinct peaks at 2.5 and 8 h after dosing. The major metabolite present in the blood at all times was unconjugated p-hydroxymethamphetamine. 2. Biliary excretion of radioactivity after oral administration of [3H]methamphetamine to rats was about 30% dose in 24h. The major metabolite in the bile was p-hydroxymethamphetamine glucuronide. 3. Blood and bile were collected simultaneously from a rat fitted with a T-tube cannula in the common bile duct, and time-courses of blood and bile concn. of the drug and metabolites were investigated. The observation of two peaks in both blood and bile indicates enterohepatic circulation of the drug and metabolites.

Administration, Oral↗

PubMed1999

Three fatalities involving phosphine gas, produced as a result of methamphetamine manufacturing.

In August of 1996, Sheriff's deputies investigated the deaths of three individuals suspected to have been overcome by phosphine gas. Phosphine is an extremely toxic gas, and is generally seen in the farming industry where it is used as a grain fumigant. It can also be generated as a by-product during the manufacturing of methamphetamine. Chemicals and equipment consistent with the manufacturing of methamphetamine were noted at the location, as well as an apparent reaction mixture heated to near dryness. Dräger tubes detected an atmospheric phosphine concentration in excess of 0.3 parts per million (ppm), the Threshold Limit Value. Deputies had initially assessed the scene with no protective equipment, raising concerns about phosphine toxicity and the effects of exposure. The objectives of this paper are to describe how phosphine is formed during the manufacture of methamphetamine, to review the toxicity, health effects and symptoms of exposure, to address the safety concerns regarding potential exposure to law enforcement personnel, and to describe the protective equipment available for personnel who respond to clandestine laboratories.

Adult↗

PubMed2001

Comparison of ELISAs for opiates, methamphetamine, cocaine metabolite, benzodiazepines, phencyclidine, and cannabinoids in whole blood and urine.

BACKGROUND: ELISAs are widely utilized in forensic drug analysis. A comparative assessment of microtiter plate assays for the detection of six common classes of drug in blood and urine is described. METHODS: ELISAs for opiates, methamphetamine, benzodiazepines, cocaine metabolite, phencyclidine (PCP), and tetrahydrocannabinol (THC) metabolite were evaluated in a side-by-side study. The analytical performance of 12 commercially available ELISAs was determined in terms of binding characteristics, dose-response curves, limits of detection, sensitivity, intra- and interassay imprecision, and lot-to-lot reproducibility. Assay performance was also compared using 855 forensic casework samples. RESULTS: Detection limits in whole blood for morphine, D-methamphetamine, nordiazepam, benzoylecgonine, nordiazepam, PCP, and L-11-nor-9-carboxy-delta9-THC were 3, 2, <4, 5, 25, and 3 microg/L, respectively, for the STC ELISAs. Corresponding detection limits for Immunalysis ELISAs were <1, <2, <4, 5, <1, and 1 microg/L, respectively. Intraassay CVs (n = 8) at the immunoassay cutoff concentrations were 4.1-5.6% and 3.5-11% for STC and Immunalysis ELISAs, respectively. Corresponding interassay CVs were 3.1-10% and 6.5-20%. Of the 855 casework samples, there were a total of 92 discordant results (44 cannabinoid, 15 opiate, 15 methamphetamine, 11 benzodiazepine, and 7 cocaine metabolite). Gas chromatography-mass spectrometry analysis indicated a total of three unconfirmed positive results for Immunalysis assays and one unconfirmed positive for STC assays. CONCLUSIONS: A comparative assessment of drugs-of-abuse assays from two manufacturers indicated some key differences in analytical performance. Overall, Immunalysis assays offered superior binding characteristics and detection limits, whereas STC assays offered improved overall precision and lot-to-lot reproducibility.

Benzodiazepines↗

PubMed1975

Effects of methamphetamine on the isolated rat phrenic nerve-diaphragm preparation.

Low concentrations of methamphetamine facilitated twitch, while higher concentrations produced dose-dependent blockade of twitch indirectly elicited. Methamphetamine facilitated twitch elicited by direct stimulation; These findings suggest that methamphetamine-induced enhancement in physical endurance and performance in moderate doses, and muscle weakness at high doses, may be attributed to drug effects at a peripheral site of action.

Animals↗