Dissociable deficits in the decision-making cognition of chronic amphetamine abusers, opiate abusers, patients with focal damage to prefrontal cortex, and tryptophan-depleted normal volunteers: evidence for monoaminergic mechanisms. (1/547)

We used a novel computerized decision-making task to compare the decision-making behavior of chronic amphetamine abusers, chronic opiate abusers, and patients with focal lesions of orbital prefrontal cortex (PFC) or dorsolateral/medial PFC. We also assessed the effects of reducing central 5-hydroxytryptamine (5-HT) activity using a tryptophan-depleting amino acid drink in normal volunteers. Chronic amphetamine abusers showed suboptimal decisions (correlated with years of abuse), and deliberated for significantly longer before making their choices. The opiate abusers exhibited only the second of these behavioral changes. Importantly, both sub-optimal choices and increased deliberation times were evident in the patients with damage to orbitofrontal PFC but not other sectors of PFC. Qualitatively, the performance of the subjects with lowered plasma tryptophan was similar to that associated with amphetamine abuse, consistent with recent reports of depleted 5-HT in the orbital regions of PFC of methamphetamine abusers. Overall, these data suggest that chronic amphetamine abusers show similar decision-making deficits to those seen after focal damage to orbitofrontal PFC. These deficits may reflect altered neuromodulation of the orbitofrontal PFC and interconnected limbic-striatal systems by both the ascending 5-HT and mesocortical dopamine (DA) projections.  (+info)

Methamphetamine abuse and emergency department utilization. (2/547)

Methamphetamine (MAP) abuse continues to increase worldwide, based on morbidity, mortality, drug treatment, and epidemiologic studies and surveys. MAP abuse has become a significant health care, environmental, and law enforcement problem. Acute intoxication often results in agitation, violence, and death. Chronic use may lead to infection, heart failure, malnutrition, and permanent psychiatric illness. MAP users frequently use the emergency department (ED) for their medical care. Over a 6-month period we studied the demographics, type, and frequency of medical and traumatic problems in 461 MAP patients presenting to our ED, which serves an area noted for high levels of MAP production and consumption. Comparison was made to the general ED population to assess use patterns. MAP patients were most commonly Caucasian males who lacked health insurance. Compared to other ED patients during this time, MAP patients used ambulance transport more and were more likely to be admitted to the hospital. There was a significant association between trauma and MAP use in this patient population. Our data suggest MAP users utilize prehospital and hospital resources at levels higher than the average ED population. Based on current trends, we can expect more ED visits by MAP users in the future.  (+info)

Methamphetamine and the expanding complications of amphetamines. (3/547)

During the past 10 years, the use of methamphetamine has increased rapidly in the West and throughout the United States. Because of this increase, our attention has focused on methamphetamine's toxicity. Methamphetamine and related compounds generate many of the same toxic effects as cocaine. Because of methamphetamine's widespread use, clinicians should be familiar with its medical effects and toxicity and with treatment options for acute and long-term effects of methamphetamine abuse.  (+info)

Amphetamine withdrawal alters bistable states and cellular coupling in rat prefrontal cortex and nucleus accumbens neurons recorded in vivo. (4/547)

Repeated amphetamine administration is known to produce changes in corticoaccumbens function that persist beyond termination of drug administration. We have found previously that long-term alteration in dopamine systems leads to changes in gap junction communication, expressed as dye coupling, between striatal neurons. In this study, the cellular bases of amphetamine-induced changes were examined using in vivo intracellular recordings and dye injection in ventral prefrontal-accumbens system neurons of control and amphetamine-treated rats. Rats that had been withdrawn from repeated amphetamine displayed a significant increase in the incidence of dye coupling in the prefrontal cortex and nucleus accumbens, which persisted for up to 28 d after withdrawal. The increased coupling was limited to projection neurons in both prefrontal cortical and accumbens brain regions, as identified by their axonal trajectory or the absence of interneuron-selective immunocytochemical markers. These changes occurred with no substantial loss of tyrosine hydroxylase-immunoreactive terminals in these cortical and accumbens regions, ruling out dopamine degeneration as a precipitating factor. Previous studies showed that nitric oxide plays a role in the regulation of coupling; however, amphetamine-withdrawn rats had fewer numbers of neurons and processes that stained for nitric oxide synthase immunoreactivity. In amphetamine-treated rats, a higher proportion of cortical cells fired in bursts, and a larger proportion of accumbens and prefrontal cortical neurons exhibited bistable membrane oscillations. By increasing corticoaccumbens transmission, amphetamine withdrawal may lead to neuronal synchronization via gap junctions. Furthermore, this adaptation to amphetamine treatment persists long after the drug is withdrawn.  (+info)

Effects of isradipine, a dihydropyridine-class calcium channel antagonist, on D-methamphetamine-induced cognitive and physiological changes in humans. (5/547)

D-methamphetamine is abused for its euphoric effects and stimulatory action on cognitive function. Its abuse can, however, be associated with massive hypertension resulting in strokes, ruptured aneurysms, or myocardial infarction. We examined the utility of isradipine, a dihydropyridine-class calcium channel antagonist, in treating d-methamphetamine induced hypertension and evaluated its effects on cognitive function, both of which are mediated by dopaminergic mechanisms. D-methamphetamine dose-dependently increased all vital signs (systolic, diastolic, and mean arterial pressure, and pulse rate) parameters. Isradipine significantly reduced d-methamphetamine-induced increases in diastolic and mean arterial pressure; however, this potentially beneficial therapeutic effect was offset by a significant reflex rise in pulse rate. D-methamphetamine also improved attention, accuracy of reasoning ability, and performance on computerized cognitive function tasks. D-methamphetamine's cognitive improving effects were not altered significantly by isradipine. Isradipine increased the false responding rate but was without significant effect on any other attentional task, or on reasoning ability, or performance. Isradipine does not appear to enhance cognitive function in healthy humans.  (+info)

Acute psychological effects of 3,4-methylenedioxymethamphetamine (MDMA, "Ecstasy") are attenuated by the serotonin uptake inhibitor citalopram. (6/547)

3,4-Methylenedioxymethamphetamine (MDMA, "Ecstasy") is a recreational drug that has been shown to release serotonin (5-HT) and dopamine (DA) in animals. The effect of MDMA on 5-HT release can be blocked by 5-HT uptake inhibitors such as citalopram, suggesting that MDMA interacts with the 5-HT uptake site. It is unknown whether this mechanism is also responsible for the psychological effects of MDMA in humans. We investigated the effect of citalopram pretreatment (40 mg iv) on the psychological effects of MDMA (1.5 mg/kg po) in a double-blind placebo-controlled psychometric study in 16 healthy human volunteers. MDMA produced an emotional state with heightened mood, increased self-confidence and extroversion, moderate derealization, and an intensification of sensory perception. Most of these effects were markedly reduced by citalopram. This finding suggests that the psychological effects of MDMA are mediated via action at the 5-HT uptake site to increase 5-HT release through the carrier, as expected from animal studies.  (+info)

Carbamazepine suppresses methamphetamine-induced Fos expression in a regionally specific manner in the rat brain. Possible neural substrates responsible for antimanic effects of mood stabilizers. (7/547)

Carbamazepine (CBZ) has been widely used for treatment of manic states. Because amphetamine produces effects in humans similar to those of idiopathic mania, acute methamphetamine administration could serve as a model of this condition. To elucidate the neurobiological substrates responsible for the antimanic effects of carbamazepine, this study investigated the effects of chronic carbamazepine administration on regional Fos protein expression induced by a single dose of methamphetamine (2mg/kg). Chronic treatment with CBZ (0.25% in food for 7 days, followed by 0.5% for 7 days; final mean serum carbamazepine concentration: 4.09 +/- 0.34 microg/ml) significantly attenuated the number of Fos-like immunoreactivity-positive nuclei induced by methamphetamine administration in the core of the nucleus accumbens and the caudate/putamen. The results indicate these brain regions are involved in the antimanic effects of carbamazepine.  (+info)

Substance abuse and the kidney. (8/547)

Substance abuse has been increasing steadily in the UK and some other countries. Recent evidence suggests more than 40% of young people have tried illicit drugs at some time. There are numerous medical consequences to recreational drug use, and a physician should always consider substance abuse in any unexplained illness. The renal complications of drug abuse are also becoming more frequent, and may encompass a spectrum of glomerular, interstitial and vascular diseases. Although some substances are directly nephrotoxic, a number of other mechanisms are also involved. These effects are often chronic and irreversible, but occasionally acute with possible recovery. The rapid growth of illicit drug use is clearly a major public health problem. We review the commonly used substances of abuse and their associations with renal disease.  (+info)