Chronic Methamphetamine Abuse Research Articles

Deficits in response inhibition associated with chronic methamphetamine abuse

Chronic methamphetamine (MA) abuse is associated with cerebral deficits, involving frontal/basal-ganglia regions that are important for inhibitory control. We used the Stop-Signal Task to measure response inhibition in 11 MA abusers (5–7 days abstinent) and two groups of control subjects who did not use MA (14 tobacco smokers and 29 non-smokers). Stop-signal reaction time (SSRT), which indicates the latency to inhibit an initiated motor response, was significantly longer for MA abusers than for either control group ( p's < .01). In contrast, the MA abusers did not differ from either group on Go trial reaction time (RT) or number of discrimination errors, which reflect motor speed and decision-processes, respectively. MA abuse in this study was therefore associated with a specific deficit in inhibiting a pre-potent response. Future research could examine whether SSRT is different for MA abusers who respond to treatment compared to those who do not. If such differences are established then response inhibition may serve as a marker for investigating MA abuse in basic science and clinical trials.

Structural abnormalities in the brains of human subjects who use methamphetamine.

We visualize, for the first time, the profile of structural deficits in the human brain associated with chronic methamphetamine (MA) abuse. Studies of human subjects who have used MA chronically have revealed deficits in dopaminergic and serotonergic systems and cerebral metabolic abnormalities. Using magnetic resonance imaging (MRI) and new computational brain-mapping techniques, we determined the pattern of structural brain alterations associated with chronic MA abuse in human subjects and related these deficits to cognitive impairment. We used high-resolution MRI and surface-based computational image analyses to map regional abnormalities in the cortex, hippocampus, white matter, and ventricles in 22 human subjects who used MA and 21 age-matched, healthy controls. Cortical maps revealed severe gray-matter deficits in the cingulate, limbic, and paralimbic cortices of MA abusers (averaging 11.3% below control; p < 0.05). On average, MA abusers had 7.8% smaller hippocampal volumes than control subjects (p < 0.01; left, p = 0.01; right, p < 0.05) and significant white-matter hypertrophy (7.0%; p < 0.01). Hippocampal deficits were mapped and correlated with memory performance on a word-recall test (p < 0.05). MRI-based maps suggest that chronic methamphetamine abuse causes a selective pattern of cerebral deterioration that contributes to impaired memory performance. MA may selectively damage the medial temporal lobe and, consistent with metabolic studies, the cingulate-limbic cortex, inducing neuroadaptation, neuropil reduction, or cell death. Prominent white-matter hypertrophy may result from altered myelination and adaptive glial changes, including gliosis secondary to neuronal damage. These brain substrates may help account for the symptoms of MA abuse, providing therapeutic targets for drug-induced brain injury.

Chronic methamphetamine increases fighting in mice

A propensity for violent behaviors to develop in chronic methamphetamine (METH) abusers has been noted. The idea that increased aggressiveness might result from chronic METH administration was tested in mice after chronic (long-term intermittent, 8 weeks) or single exposures to the drug. A single injection of METH (6 mg/kg) did not augment fighting. In contrast, chronic METH administration significantly increased the number of animals that initiated bite attacks. This regimen also shortened the latency before the first attack. Latency before the first attack was shorter at 20 h after the METH injection than at 15 min after injection. Locomotor activity was not different at 20 h after METH injection, indicating that increased fighting was not secondary to METH-induced hyperactivity. METH-induced increases in fighting were not related to the duration of persistent sniffing after the initial encounter with an intruder since the duration of this behavior was significantly increased at 15 min after METH but not at 20 h post drug. These results indicate that repeated injections of METH can increase fighting behaviors and also alter social interactions in mice. Thus, intermittent administration of METH might be useful as a pharmacological model to study the biochemical and molecular bases of aggressiveness.

Preliminary evidence of reduced cognitive inhibition in methamphetamine-dependent individuals

Chronic methamphetamine abuse is associated with disruption of frontostriatal function involving serotonin and dopamine circuitry. Clinically, methamphetamine-dependent (MD) individuals are highly distractible and have difficulty focussing. Here, we used a computerized single-trial version of the Stroop Test to examine selective attention and priming in MD. Subject groups comprised eight MD men (31.7±7.2 years of age), who had used methamphetamine for 15.75±8.4 years but were currently abstinent for 2–4 months, and 12 controls (35.7+9.7 years of age). Compared with the control group, the MD group exhibited significantly greater interference ( P<0.05) despite intact priming. Error rates did not differ between the groups. This preliminary finding of reduced cognitive inhibition in MD individuals is consistent with the distractibility they show clinically. Furthermore, the dissociation between explicit attentional performance and priming effects suggests that some attentional functions are not as affected by long-term methamphetamine use as others.

Determination of chronic methamphetamine abuse by hair analysis

A 30-year-old male truck driver, known to be asthmatic, was found dead at the roadside lying near his car. A nebulizer bottle of Berotec (fenoterol hydrobromide) was found near his hand. The anatomic cause of death was suspected to be asthma. Toxicological screening of urine using Triage demonstrated the presence of methamphetamine. The blood concentration of methamphetamine was 0.4 μg/ml, and fenoterol was not detected. Hair analysis clearly indicated chronic methamphetamine abuse and medium dependency during the 2 months before death. We conclude that death might have been induced by the interaction of fenoterol and methamphetamine.

Transient increases of histamine H 1 and H 2 receptor mRNA levels in the rat striatum after the chronic administration of methamphetamine

In our previous studies, we found that behavioral sensitization evoked by repeated administration of methamphetamine (METH) was suppressed by the activation of the histaminergic neuron system in the brain. In continuation of these studies, we measured the levels of H 1 and H 2 receptor mRNAs in the rat striatum by semi-quantitative reverse transcription-polymerase chain reaction. Seven days after the 21 consecutive administrations of METH (4 mg/kg, i.p.), the levels of both H 1 and H 2 receptor mRNAs in the rat striatum increased significantly. However, 1 and 14 days after the last administration, there were no significant changes in levels of either H 1 or H 2 receptor mRNA in the rat striatum. These transient increases of H 1 and H 2 receptor mRNAs may have some relation to chronic METH abuse and its withdrawal.

Abnormal cerebral perfusion in chronic methamphetamine abusers: A study using 99mTC-HMPAO and spect

1. 1. Cerebral blood flow of nine methamphetamine abusers with technetium-99m-hexamethyl-propyleneamine oxime (HMPAO) and single photon emission computed tomography (SPECT) as well as morphological examination with magnetic resonance imaging (MRI) were investigated. 2. 2. Six of these subjects exhibited multiple focal perfusion deficits in cerebral cortices without abnormalities in MRI including cerebral atrophy and/or infarctions. 3. 3. Cerebral perfusion deficits were detected in methamphetamine abusers even after a long abstinence period, suggesting that vascular changes were irreversible to some degree. 4. 4. HMPAO SPECT study appeared to be sensitive to the detection of cerebral perfusion abnormalities in drug abusers.

A histopathological study of pancreatic lesions after chronic administration of methamphetamine to rats.

The effects of chronic administration of methamphetamine on pancreatic tissues were histopathologically studied in experimental models. Methamphetamine (1 ml/kg body weight/day) was subcutaneously injected into 14 five-week-old male Wistar Kyoto rats (WKY) for 12 weeks. Age and sex matched 5 WKY rats served as controls. With light microscopy, some scattered edematous lesions and moderate vacuolization were demonstrated in the pancreas of 8 of the methamphetamine treated rats. However, in 4 of the rats, severe regional hemorrhage, partial acinal cell necrosis, destruction of the acinal cells, neutrophile infiltration, interstitial vessel dilatation, interstitial edema and fatty cell invasion were observed after the injections of methamphetamine. In 2 other animals, fibrosis and cirrhosis-like lesions with destruction and degeneration of the acinal cells were observed the small vessels had a slight degeneration of the endothelial cells. In the control animals, no lesions, except for some edematous lesions were found. In all cases, there were no nesidioblastosis-like lesions or necrosis of the Langerhans's islets. In the immunohistochemical study using anti- alpha 1-chymotrypsin antibody, more positive reactive cells were demonstrated among the interstitial and inter acinal cells, both in number and degree, in the methamphetamine treated rats. In addition to the animal model, there were 4 autopsy cases of sudden death in chronic methamphetamine abusers. The autopsies demonstrated a severe acute necrotic hemorrhagic pancreatitis, with only scattered slight hemorrhaging in the brain and lungs. These findings indicate that chronic administration of methamphetamine to rats evoked significant changes in pancreatic tissues including some degeneration of the endothelial cells of the small vessels in this hypoxia-vulnerable organ.