Oxytocin increases physiological linkage during group therapy for methamphetamine use disorder: a randomized clinical trial.

Patients and psychotherapists often exhibit behavioral, psychological, and physiological similarity. Here, we test whether oxytocin-a neuropeptide that can enhance expressivity and social perception-influences time-lagged "linkage" of autonomic nervous system responses among participants and facilitators during group therapy. Physiological linkage estimates (n = 949) were created from ten cohorts, each with two facilitators (n = 5) and four to six participants (n = 48), over six weekly sessions of group therapy for methamphetamine use disorder. All participants of a cohort received oxytocin or placebo intranasally in a randomized double-blind procedure before each session. Cardiac interbeat intervals (IBI) were measured continuously during sessions to estimate physiological linkage, operationalized as one cohort-mate's IBI reactivity during one minute predicting another cohort-mate's IBI reactivity during the following minute. In oxytocin cohorts, participants and facilitators experienced significant physiological linkage to their cohort-mates (i.e., their physiological responses were predicted by the prior responses of their cohort-mates) and significantly more linkage than people in placebo cohorts. Both effects occurred during the first and second sessions but not later sessions. Results suggest that oxytocin may enhance psychosocial processes often associated with linkage-such as social engagement-in groups and highlight oxytocin's potential to improve group cohesion during group therapy.Clinical Trials Registration: NCT02881177, First published on 26/08/2016.

Changes of BDNF exon IV DNA methylation are associated with methamphetamine dependence.

Aim: We investigated DNA methylation of BDNF in methamphetamine (METH) dependence in humans and an animal model. Materials & methods:BDNF methylation at exon IV was determined by pyrosequencing of blood DNA from METH-dependent and control subjects, and from rat brain following an escalating dose of METH or vehicle. Bdnf expression was determined in rat brain. Results:BDNF methylation was increased in human METH dependence, greatest in subjects with psychosis and in prefrontal cortex of METH-administered rats; rat hippocampus showed reduced Bdnf methylation and increased gene expression. Conclusion:BDNF methylation is abnormal in human METH dependence, especially METH-dependent psychosis, and in METH-administered rats. This may influence BDNF expression and contribute to the neurotoxic effects of METH exposure.

Lay abstract The effects of methamphetamine (METH), an addictive psychostimulant drug, on changes of DNA methylation of an important regulator of neuronal survival, BDNF, were examined in blood of METH-dependent patients and in the brain of METH-administered rats. BDNF methylation was increased in patients and in the prefrontal cortex of METH-administered rats, while rat hippocampus showed a reduction of Bdnf methylation, with an equivalent increase in gene expression. The methylation increases in humans were greatest in those with a METH-induced psychosis. Although a relationship between Bdnf methylation and its expression has not been proven, changes of BDNF DNA methylation are associated with METH dependence, especially METH-dependent psychosis, suggesting that METH neurotoxicity may relate to the effects of changes in BDNF methylation.

The exploration of optimized protocol for repetitive transcranial magnetic stimulation in the treatment of methamphetamine use disorder: A randomized sham-controlled study.

BACKGROUND: The prefrontal-striatal circuit is a core circuit related to substance dependence. Previous studies have found that repetitive transcranial magnetic stimulation (rTMS) targeting the dorsolateral prefrontal cortex (DLPFC) (key region of executive network) had limited responses, while inhibiting hyperactivation of ventromedial prefrontal cortex (vmPFC) (key region of limbic network) may be another strategy. However, there is currently no comparison between these two treatment locations. METHODS: Seventy-four methamphetamine-dependent patients were randomly assigned to one of treatment groups with two-week treatment: (1) Group A: intermittent theta-burst stimulation (iTBS) targeting the left DLPFC; (2) Group B: continuous theta-burst stimulation (cTBS) targeting the left vmPFC; (3) Group C: a combination of treatment protocol of Group A and Group B; (4) Group D: sham theta-burst stimulation. The primary endpoint was the change of cue-induced craving. The trial was registered at ClinicalTrials.gov (NCT03736317). FINDINGS: The three real TBS groups had more craving decrease effect than the sham group (p<0.01). The changes of craving were positively correlated with the improvement of anxiety and withdrawal symptom. With the highest respondence rate, group C also had shorter respondence time than Group A (p = 0.03). Group C was effective in improve depression symptoms (p = 0.04) and withdrawal symptom (p = 0.02) compared with Group D. Besides, Group C was significant in improve sleep quality (p = 0.04) compared with Group A. Baseline depression scores and spatial working memory were positively predicting the intervention response. INTERPRETATION: The rTMS paradigms involving vmPFC with cTBS are optimized protocols and well-tolerated for methamphetamine-dependent individuals, and they may have better efficacies compared with DLPFC iTBS. Emotion and cognitive function are rTMS treatment response predictors for methamphetamine-dependent patients. FUNDING: This work was supported by the National Key R&D Program of China (2017YFC1310400), National Natural Science Foundation of China (81,771,436, 81,801,319, 81,601,164), Shanghai Municipal Health and Family Planning Commission (2017ZZ02021), Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai (2017YQ013), Qihang Project of Shanghai Mental Health Center (2019-QH-05), Shanghai Sailing Program (19YF1442100), Shanghai Key Laboratory of Psychotic Disorders (13DZ2260500), Program of Shanghai Academic Research Leader (17XD1403300), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05), and Shanghai Clinical Research Center for Mental Health (19MC1911100).

Assessment of Amphetamine Withdrawal Symptoms of Lisdexamfetamine Dimesylate Treatment for Adults With Binge-Eating Disorder.

OBJECTIVE: To determine whether physical dependence developed during lisdexamfetamine dimesylate treatment, as evidenced by presence of withdrawal symptoms after treatment cessation in adults with binge-eating disorder (BED) treated for up to 38 weeks. METHODS: Three studies enrolled adults with DSM-IV-TR-defined BED. In two 12-week, randomized, double-blind, placebo-controlled studies conducted from November 2012 to September 2013, participants were treated with placebo or dose-optimized lisdexamfetamine (50 or 70 mg). In a double-blind, placebo-controlled, randomized-withdrawal maintenance-of-efficacy study conducted from January 2014 to April 2015, participants categorized as responders after 12 weeks of open-label lisdexamfetamine (50 or 70 mg) were randomized to continued lisdexamfetamine or placebo for 26 weeks. The Amphetamine Cessation Symptom Assessment (ACSA), a 16-item self-report instrument (total score: 0-64), assessed withdrawal experiences. Mean ± SD ACSA scores and medians are presented for study completers. RESULTS: In the short-term efficacy studies, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine (pooled data) were 7.0 ± 7.60 (n = 275) and 4.9 ± 6.41 (n = 271), respectively, on the day of the last dose at week 12/early termination (ET) and 4.8 ± 6.82 (n = 234) and 5.5 ± 7.50 (n = 221) on day 7 after the last dose. In the maintenance-of-efficacy study, mean ± SD ACSA aggregate scores for placebo and lisdexamfetamine were 4.8 ± 6.67 (n = 44) and 4.7 ± 7.78 (n = 85) on the day of the last dose at week 38/ET and 3.9 ± 5.75 (n = 37) and 5.2 ± 7.93 (n = 71) on day 7 after the last dose. CONCLUSIONS: Study results suggest that abrupt lisdexamfetamine termination was not associated with amphetamine withdrawal symptoms at the exposure durations and therapeutic doses analyzed. TRIAL REGISTRATION: Clinicaltrials.gov identifiers: NCT01718483, NCT01718509, and NCT02009163.

Are sweetened drinks a gateway to alcohol, opiate and stimulant addiction? Summary of evidence and therapeutic strategies.

1. Drinks sweetened with both sugar and artificial additives lead to dopamine release at the nucleus accumbens (NAc) in rat models; the basis of experiences of pleasure in humans, resulting in impulsive binging behaviour at times. 2. Evidence from rat models show cross sensitisation between sweetened drinks, alcohol, opiates and stimulants. Therefore, it could be hypothesised that sweetened drinks could be a gateway to multiple substance abuse among humans via 'alcopops'. 3. Identification of an allelic variant of the cyclic adenosine monophosphate responsive element modulator gene (CREM), linking impulsivity and multiple substance abuse, opens up prospects of mass screening to advice on harm reduction. 4. Furthermore, therapies involving cannabinoid receptor antagonists and transcranial brain stimulation are being currently investigated; of benefit to limit binge use of sweetened drinks.

An association study between methamphetamine use disorder with psychosis and polymorphisms in MiRNA.

BACKGROUND: Methamphetamine (MA) is an addictive psychostimulant substance that mainly leads to schizophrenia-like psychotic symptoms. The expression of miRNAs in brain plays an important role in neurological disorders and may affect by genetic variant(s) in the target site (MiRSNPs). In this study, we investigated whether polymorphisms in miRNAs are associated with MA disorder with psychosis. METHODS: We carried out a case-control association study in 400 MA users with psychotic characters and 448 controls. Six MiRSNPs with predicted functional relevance miRNAs (miR-181b, miR-181a, miR-15b, miR-let-7e and miRlet-7d) were selected for genotyping. Allele and genotype frequencies were compared between MA users and healthy individuals. The expression of five miRNAs were measured by quantitative real-time RT-PCR in 55 cases and 57 controls. We also explored an expression Quantitative Trait Loci (eQTL) analysis based on the miRNAs expression and SNP genotype. RESULTS: The SNP rs10760371 within miR-181a was nominally associated with MA disorder (P = 0.046). For rs1099308, rs10760371 and rs10993081 in strong linkage disequilibrium (LD), no significant association had been detected from haplotype analysis. Discrepancy had been found between MA users and healthy individuals (P < 0.01) in terms of the expression of miR-181a, miR-15b, miR-let-7e and miR-let-7d. and no noticeable difference had been found from the eQTL analysis. CONCLUSION: Our findings suggest that rs10760371 within miR-181a may relate to the development of MA dependence with psychosis. The miRNAs expression is unlikely to be regulated by the SNPs within it.

Methamphetamine-associated difficulties in cognitive control allocation may normalize after prolonged abstinence.

Chronic heavy methamphetamine use likely causes dopaminergic neurotoxicity, which is commonly thought to result in cognitive control deficits. Both of these alterations may persist even after the use is discontinued, but tend to (partly) improve with increasing duration of abstinence. While several studies have demonstrated that the reinstatement of comparatively normal dopaminergic signaling may take months, if not years, the amelioration of cognitive deficits has predominantly been investigated in much shorter intervals of several weeks to less than half a year. Against this background, we set out to investigate the effects on prolonged abstinence in n = 27 abstinent former methamphetamine users in a cross-sectional design using behavioral and neurophysiological measures of cognitive control. Our behavioral results suggest that former users struggled to identify and adapt to different degrees of cognitive control requirements, which made their behavioral performance less expedient than that of healthy controls. On the neurophysiological level, this was reflected by reduced modulations of the N2-N450 amplitude in response to high vs. low cognitive control requirements. Yet, those effects could only be observed in methamphetamine users who had been abstinent for a relatively short time (mean 9.9; max. 18 months), but not in former users who had been abstinent two years or longer. While this finding alone does not allow for causal inferences, it suggests that the amelioration of control deficits may take longer than what is commonly investigated (1-6 months). Hence, some of the statements about permanent/irreversible dopamine-dependent executive dysfunctions in former methamphetamine users should be interpreted with caution.

Review of long-term consequences of maternal methamphetamine exposure.

Methamphetamine is one of the most abused hard drugs in the Czech Republic. Its popularity is high not only in Eastern Bloc of Europe but is growing in other countries around the world, including the United States. In addition, methamphetamine abuse increases in drug addicts during pregnancy. Although research into the long-term effects of prenatal methamphetamine exposure has been ongoing for many years, the exact mechanism of action and factors that may influence the effect of this drug are still not fully understood. There have been many studies that investigated the effects of addictive substances on the behavior and cognitive function of individuals during adolescence. Some studies have shown prenatal or perinatal influences, e.g. drugs, stress, hypoxia, and malnutrition, can affect drug sensitivity or drug-seeking behavior in adulthood. However, when these factors are most impactful, i.e. prenatal vs. perinatal, and which stages of the prenatal and perinatal periods are the most sensitive to these factors is not yet clear. Our laboratory specializes in research on the effects of drugs (especially methamphetamine) on rat mothers and their offspring during postnatal development, adolescence, and adulthood. This review summarizes our past results on the long-term effects of methamphetamine on the mother and her offspring, its mechanism of action, the role of maternal care, the possible emergence of long-term sensitization, and the critical neurodevelopmental periods for methamphetamine exposure.

The relationship between impulsivity and methamphetamine use severity in a community sample.

BACKGROUND: Abuse of psychostimulants, including methamphetamine (MA), has been linked to heightened impulsivity. While previous research has demonstrated differences in impulsivity between MA users and non-substance users, less is known about variability in impulsivity within MA users and whether the severity of MA use related problems predicts impulsivity within individuals who regularly use MA. This study aims to elucidate the relationship between impulsivity and MA use severity. METHOD: Non-treatment seeking individuals who reported regular MA use (n = 177) completed an impulsivity battery comprising self-report and behavioral measures. A structural equation modeling (SEM) approach was used to test the relationship between the MA use related problem severity and measures of impulsivity. RESULTS: The final SEM model of impulsivity and MA use related problems (CFI = 0.897, RMSEA = 0.059, S-B scaled χ2 [260,n = 103] = 406.86) revealed that greater MA use severity was associated with greater self-reported impulsiveness, but no relationship was found between MA use severity and behavioral measures of impulsivity. CONCLUSIONS: The current findings extend previous research by providing additional evidence that MA use is associated with increased self-reported impulsivity and highlights the importance of evaluating impulsivity as a multidimensional construct.

New Scaffold for Lead Compounds to Treat Methamphetamine Use Disorders.

Despite increased methamphetamine use worldwide, pharmacotherapies are not available to treat methamphetamine use disorder. The vesicular monoamine transporter-2 (VMAT2) is an important pharmacological target for discovery of treatments for methamphetamine use disorder. VMAT2 inhibition by the natural product, lobeline, reduced methamphetamine-evoked dopamine release, methamphetamine-induced hyperlocomotion, and methamphetamine self-administration in rats. Compared to lobeline, lobelane exhibited improved affinity and selectivity for VMAT2 over nicotinic acetylcholine receptors. Lobelane inhibited neurochemical and behavioral effects of methamphetamine, but tolerance developed to its behavioral efficacy in reducing methamphetamine self-administration, preventing further development. The lobelane analog, R-N-(1,2-dihydroxypropyl)-2,6-cis-di-(4-methoxyphenethyl)piperidine hydrochloride (GZ-793A), potently and selectively inhibited VMAT2 function and reduced neurochemical and behavioral effects of methamphetamine. However, GZ-793A exhibited potential to induce ventricular arrhythmias interacting with human-ether-a-go-go (hERG) channels. Herein, a new lead, R-3-(4-methoxyphenyl)-N-(1-phenylpropan-2-yl)propan-1-amine (GZ-11610), from the novel scaffold (N-alkyl(1-methyl-2-phenylethyl)amine) was evaluated as a VMAT2 inhibitor and potential therapeutic for methamphetamine use disorder. GZ-11610 was 290-fold selective for VMAT2 over dopamine transporters, suggesting that it may lack abuse liability. GZ-11610 was 640- to 3500-fold selective for VMAT2 over serotonin transporters and nicotinic acetylcholine receptors. GZ-11610 exhibited > 1000-fold selectivity for VMAT2 over hERG, representing a robust improvement relative to our previous VMAT2 inhibitors. GZ-11610 (3-30 mg/kg, s.c. or 56-300 mg/kg, oral) reduced methamphetamine-induced hyperactivity in methamphetamine-sensitized rats. Thus, GZ-11610 is a potent and selective inhibitor of VMAT2, may have low abuse liability and low cardiotoxicity, and after oral administration is effective and specific in inhibiting the locomotor stimulant effects of methamphetamine, suggesting further investigation as a potential therapeutic for methamphetamine use disorder.

Rapid detection of methamphetamine in human fingernails by liquid-liquid extraction method and one-step methamphetamine test strip.

Background: Methamphetamine cannot be detected through conventional urine screening tests or other analytical methods in methamphetamine abusers who have not used the drug for some time. In some instances, detection of methamphetamine in fingernails can be a good alternative. We aimed to determine the sensitivity and specificity of the one-step methamphetamine test strip used in the detection of methamphetamine in urine in the detection of methamphetamine in fingernails. Methods: We took 72 fingernail samples, including 60 samples from methamphetamine abusers and 12 samples as controls from their relatives who had no history of methamphetamine use. The liquid-liquid extraction method was used on fingernail samples, and the resultant solution was tested with one-step methamphetamine test strip. We analysed participants' demographics including age, gender, duration of methamphetamine abuse and strip test results. Results: The mean (SD) age of the participants was 25 (4.33) years. The mean (SD) duration of methamphetamine abuse was 10 (4.5) months. Of the 72 participants, 61 (84.7%) had positive and 11 (15.3%) had negative strip test results. All 60 methamphetamine abusers had positive test results. A positive or negative history of methamphetamine abuse was taken as the gold standard. The sensitivity and specificity of the test was 100% and 91.6%, respectively. Conclusion: Performing liquid-liquid extraction on fingernails and using the strip test for detection of methamphetamine is a simple, inexpensive, rapid and accessible method, and its high sensitivity and specificity make it appropriate for screening. This method may be preferred over other urine and blood methamphetamine detection methods when the patient has not used the drug for a few days.

Prior binge-drinking history promotes the positive affective valence of methamphetamine in mice.

An alcohol use disorder is a major predisposing factor for methamphetamine (MA) abuse. Further, MA-alcohol co-abuse is a risk factor for treatment discontinuation and non-compliance in MA-dependent individuals. No effective treatment exists for MA addiction, let alone treatments directed at those suffering from MA-alcohol addiction co-morbidity. Thus, it is imperative that we develop high-throughput animal models to study the biobehavioral interactions between MA and alcohol of relevance to the etiology and treatment of co-abuse. To this end, we reported that a history of binge alcohol-drinking [5,10, 20 and 40% (v/v); 2 h/day for 10-14 days] reduces MA reinforcement and intake, but it augments MA-preference and intake when drug availability is behaviorally non-contingent. To reconcile this apparent discrepancy in findings, we employed a comparable 2-week binge-drinking paradigm as that employed in our previous studies followed by place-conditioning procedures (4 pairings of 0.25, 0.5, 1, 2 or 4 mg/kg MA, i.p.). This was meant to determine how a prior binge-drinking history impacts the affective valence of MA and sensitivity to MA-induced psychomotor-activation/sensitization. Prior binge-drinking history blunted spontaneous locomotor activity and shifted the MA dose-place-preference function upwards of water drinking controls. The potentiation of MA-conditioned reward by prior binge-drinking history was independent of any alcohol effects upon the locomotor-activating or -sensitizing effects of MA. Based on these results we propose that the reduced MA reinforcement reported previously by our group likely reflects a compensatory response to an increased sensitivity to MA's positive subjective effects rather than increased sensitivity to the drug's psychomotor-activating effects.

Structural factors associated with methamphetamine smoking among female sex workers in Tijuana, Mexico.

INTRODUCTION AND AIMS: Smoking methamphetamine is associated with increased risk of HIV among female sex workers (FSW). The structural context of substance use is an important shaper of individual behaviour; however, structural determinants of methamphetamine use among FSWs are largely unknown. We identified individual, structural and neighbourhood factors associated with smoking methamphetamine among FSWs in the border city of Tijuana, Baja California, Mexico. DESIGN AND METHODS: A prospective cohort of 301 FSWs sampled from indoor and outdoor sex work venues throughout Tijuana participated in quantitative surveys on behaviours and mapping of home and work neighbourhoods across three visits. Multinomial logistic regression using generalised estimating equations identified individual, structural and neighbourhood variables associated with smoking methamphetamine. RESULTS: Methamphetamine use, particularly smoking, was highly prevalent among FSWs. Over half (61%) of FSWs had ever used methamphetamine in their lifetime and at baseline, 38% currently smoked methamphetamine. Smoking methamphetamine daily was associated with living in the red light district [adjusted odds ratio (AOR) = 2.72, 95% confidence interval (CI) = 1.23-6.02] and with perceived homelessness, but only among women in a good financial situation (AOR = 4.08, 95% CI = 1.58-10.50). Smoking methamphetamine less than daily was associated with older age (AOR = 1.06, 95% CI = 1.02-1.10). DISCUSSION AND CONCLUSIONS: Our findings point to the important dynamic between the residential environment and more severe methamphetamine use. FSWs may prioritise the purchase of methamphetamine over stable housing if they have the financial means. Given the high prevalence of smoking methamphetamine among FSWs in Tijuana, drug treatment options, especially for women living in the red light district, are needed.

Structural abnormality of substantia nigra induced by methamphetamine abuse.

BACKGROUND: Methamphetamine abuse has been linked to an increased risk of Parkinson's disease. OBJECTIVE: The objective of this study was to investigate structural abnormality of the substantia nigra in past methamphetamine users using transcranial sonography. METHODS: In a cross-sectional, observational study, echogenicity of the substantia nigra was assessed in 59 past methamphetamine users and 59 matched controls. The frequencies of an abnormal spatial extension of the substantia nigra as well as the average sizes of left and right substantia nigra were evaluated. RESULTS: The average echogenic size of the substantia nigra was larger in methamphetamine users (0.22 ± 0.06 cm2 ) when compared with controls (0.17 ± 0.05 cm2 , P < .001). Furthermore, the frequency of enlarged, echogenic substantia nigra was increased in methamphetamine users (42% vs 12% in controls, P < .001). Partial correlation analysis revealed an association of echogenic substantia nigra size with estimated total lifetime intake of methamphetamine (r55 = 0.395, P = .002). CONCLUSIONS: Current data link methamphetamine abuse in humans to injury of substantia nigra neurons and an increased risk of Parkinson's disease. © 2017 International Parkinson and Movement Disorder Society.

Early Initiation of Amphetamine-Type Stimulants (ATS) Use Associated with Lowered Cognitive Performance among Individuals with Co-Occurring Opioid and ATS Use Disorders in Malaysia.

Amphetamine-type stimulants (ATS) use is increasingly prevalent in Malaysia, including among individuals who also use opioids. We evaluated cognitive functioning profiles among individuals with co-occurring opioid and ATS dependence and their lifetime patterns of drug use. Participants (N = 50) enrolling in a clinical trial of buprenorphine/naloxone treatment with or without atomoxetine completed the Raven's Standard Progressive Matrices, Rey-Osterrieth Complex Figure Test, Digit Span, Trail Making and Symbol Digit Substitution tasks. Multidimensional scaling and a K-means cluster analyses were conducted to classify participants into lower versus higher cognitive performance groups. Subsequently, analyses of variance procedures were conducted to evaluate between group differences on drug use history and demographics. Two clusters of individuals with distinct profiles of cognitive performance were identified. The age of ATS use initiation, controlling for the overall duration of drug use, was significantly earlier in the lower than in the higher cognitive performance cluster: 20.9 (95% CI: 18.0-23.8) versus 25.2 (95% CI: 22.4-28.0, p = 0.038). While adverse effects of ATS use on cognitive functioning can be particularly pronounced with younger age, potentially related to greater vulnerability of the developing brain to stimulant and/or neurotoxic effects of these drugs, the current study findings cannot preclude lowered cognitive performance before initiation of ATS use.

Two Case Studies Illustrating a Shared Decision-Making Approach to Illicit Methamphetamine Use and Breastfeeding.

Crystal methamphetamine (MA) is a potent psycho-stimulant that is increasingly used worldwide. It is highly addictive, is often made in clandestine laboratories, and can cause serious health issues in adults. Health professionals caring for women in the perinatal period must counsel women about the health risks to infants if they are exposed to MA in breast milk. Most guidelines recommend that women who have current or recent MA use do not breastfeed. This article explores approaches to breastfeeding advice in the context of MA use. Women who have made lifestyle changes, engaged well with services in the antenatal period, and are committed to drug counseling services after discharge from hospital may be supported to breastfeed if they are assessed as safe to do so. The importance of assessing each woman individually when developing infant feeding plans throughout the perinatal period is advocated.

Global motion perception is related to motor function in 4.5-year-old children born at risk of abnormal development.

Global motion perception is often used as an index of dorsal visual stream function in neurodevelopmental studies. However, the relationship between global motion perception and visuomotor control, a primary function of the dorsal stream, is unclear. We measured global motion perception (motion coherence threshold; MCT) and performance on standardized measures of motor function in 606 4.5-year-old children born at risk of abnormal neurodevelopment. Visual acuity, stereoacuity and verbal IQ were also assessed. After adjustment for verbal IQ or both visual acuity and stereoacuity, MCT was modestly, but significantly, associated with all components of motor function with the exception of fine motor scores. In a separate analysis, stereoacuity, but not visual acuity, was significantly associated with both gross and fine motor scores. These results indicate that the development of motion perception and stereoacuity are associated with motor function in pre-school children.

Heightened Dopaminergic Response to Amphetamine at the D3 Dopamine Receptor in Methamphetamine Users.

Neuroimaging studies in stimulant use (eg, cocaine, methamphetamine) disorders show that diminished dopamine release by dopamine-elevating drugs is a potential marker of relapse and suggest that increasing dopamine at the D2/3 receptors may be therapeutically beneficial. In contrast, recent investigations indicate heightened D3 receptor levels in stimulant users prompting the view that D3 antagonism may help prevent relapse. Here we tested whether a 'blunted' response to amphetamine in methamphetamine (MA) users extends to D3-rich brain areas. Fourteen MA users and 15 healthy controls completed two positron emission tomographic scans with a D3-preferring probe [11C]-(+)-PHNO at baseline and after amphetamine (0.4 mg/kg). Relative to healthy controls, MA users had greater decreases in [11C]-(+)-PHNO binding (increased dopamine release) after amphetamine in D3-rich substantia nigra (36 vs 20%, p=0.03) and globus pallidus (30 vs 17%, p=0.06), which correlated with self-reported 'drug wanting'. We did not observe a 'blunted' dopamine response to amphetamine in D2-rich striatum; however, drug use severity was negatively associated with amphetamine-induced striatal changes in [11C]-(+)-PHNO binding. Our study provides evidence that dopamine transmission in extrastriatal 'D3-areas' is not blunted but rather increased in MA users. Together with our previous finding of elevated D3 receptor level in MA users, the current observation suggests that greater dopaminergic transmission at the D3 dopamine receptor may contribute to motivation to use drugs and argues in favor of D3 antagonism as a possible therapeutic tool to reduce craving and relapse in MA addiction.