Methylphenidate improves prefrontal cortical cognitive function through α2 adrenoceptor and dopamine D1 receptor actions: Relevance to therapeutic effects in Attention Deficit Hyperactivity Disorder

BACKGROUND: Methylphenidate (MPH) is the classic treatment for Attention Deficit Hyperactivity Disorder (ADHD), yet the mechanisms underlying its therapeutic actions remain unclear. Recent studies have identified an oral, MPH dose regimen which when given to rats produces drug plasma levels similar to those measured in humans. The current study examined the effects of these low, orally-administered doses of MPH in rats performing a delayed alternation task dependent on prefrontal cortex (PFC), a brain region that is dysfunctional in ADHD, and is highly sensitive to levels of catecholamines. The receptor mechanisms underlying the enhancing effects of MPH were explored by challenging the MPH response with the noradrenergic α2 adrenoceptor antagonist, idazoxan, and the dopamine D1 antagonist, SCH23390. RESULTS: MPH produced an inverted U dose response whereby moderate doses (1.0–2.0 mg/kg, p.o.) significantly improved delayed alternation performance, while higher doses (2.0–3.0 mg/kg, p.o.) produced perseverative errors in many animals. The enhancing effects of MPH were blocked by co-administration of either the α2 adrenoceptor antagonist, idazoxan, or the dopamine D1 antagonist, SCH23390, in doses that had no effect on their own. CONCLUSION: The administration of low, oral doses of MPH to rats has effects on PFC cognitive function similar to those seen in humans and patients with ADHD. The rat can thus be used as a model for examination of neural mechanisms underlying the therapeutic effects of MPH on executive functions in humans. The efficacy of idazoxan and SCH23390 in reversing the beneficial effects of MPH indicate that both noradrenergic α2 adrenoceptor and dopamine D1 receptor stimulation contribute to cognitive-enhancing effects of MPH

A rationale and model for addressing tobacco dependence in substance abuse treatment

Most persons in drug treatment smoke cigarettes. Until drug treatment facilities systematically treat their patients' tobacco use, millions will flow through the drug treatment system, overcome their primary drug of abuse, but die prematurely from tobacco-related illnesses. This paper reviews the literature on the health benefits of quitting smoking for drug treatment patients, whether smoking causes relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and good and bad times for quitting smoking among drug treatment patients. It also presents a conceptual model and recommendations for treating tobacco in substance abuse treatment, and provides references to internet and paper-copy tools and information for treating tobacco dependence. At present, research on tobacco treatment in drug treatment is in its infancy. Although few drug treatment programs currently offer formal services, many more will likely begin to treat nicotine dependence as external forces and patient demand for these services increases. In the absence of clear guidelines and attention to quality of care, drug treatment programs may adopt smoking cessation services based on cost, convenience, or selection criteria other than efficacy. Because research in this field is relatively new, substance abuse treatment professionals should adhere to the standards of care for the general population, but be prepared to update their practices with emerging interventions that have proven to be effective for patients in drug treatment

What role does the prefrontal cortex play in the processing of negative and positive stimuli in adolescent depression?

This perspective describes the contribution of the prefrontal cortex to the symptoms of depression in adolescents and specifically the processing of positive and negative information. We also discuss how the prefrontal cortex (PFC) activity and connectivity during tasks and at rest might be a biomarker for risk for depression onset in adolescents. We include some of our recent work examining not only the anticipation and consummation of positive and negative stimuli, but also effort to gain positive and avoid negative stimuli in adolescents with depression. We find, using region of interest analyses, that the PFC is blunted in those with depression compared to controls across the different phases but in a larger sample the PFC is blunted in the anticipatory phase of the study only. Taken together, in adolescents with depression there is evidence for dysfunctional PFC activity across different studies and tasks. However, the data are limited with small sample sizes and inconsistent findings. Larger longitudinal studies with more detailed assessments of symptoms across the spectrum are needed to further evaluate the role of the PFC in adolescent depression

Sterile syringe access and disposal among injection drug users newly enrolled in methadone maintenance treatment: a cross-sectional survey

BACKGROUND: We sought to assess injection practices, means of acquiring and disposing of syringes, and utilization and knowledge of harm reduction resources among injection drug users (IDUs) entering methadone maintenance treatment (MMT). METHODS: Interviews with 100 consecutive patients, including 35 IDUs, entering a MMT program in the Bronx, NY. RESULTS: Utilization of unsafe syringe sources was reported by 69% of IDUs in our sample. Most (80%) IDUs reused syringes, and syringe sharing was also common. Fewer than half knew that non-prescription pharmacy purchase of syringes was possible. The most common means of disposing of injecting equipment were the trash (63%) and syringe exchange programs (49%). CONCLUSIONS: These findings indicate that drug users entering treatment under-utilize sanctioned venues to obtain sterile syringes or safely dispose of used injection equipment. Programs providing services to drug users should adopt a proactive stance to address the safety and health issues faced by injectors

The effects of sex and hormonal status on restraint-stress-induced working memory impairment

BACKGROUND: Restraint stress has been shown to elicit numerous effects on hippocampal function and neuronal morphology, as well as to induce dendritic remodeling in the prefrontal cortex (PFC). However, the effects of acute restraint stress on PFC cognitive function have not been investigated, despite substantial evidence that the PFC malfunctions in many stress-related disorders. METHODS: The present study examined the effects of restraint stress on PFC function in both male rats and cycling female rats in either the proestrus (high estrogen) or estrus (low estrogen) phase of the estrus cycle. Animals were restrained for 60 or 120 minutes and then tested on spatial delayed alternation, a PFC-mediated task. Performance after stress was compared to performance on a different day under no-stress conditions, and analyzed using analysis of variance (ANOVA). RESULTS: Sixty minutes of restraint impaired only females in proestrus, while 120 minutes of restraint produced significant impairments in all animals. Increases in task completion times did not affect performance. CONCLUSION: These results demonstrate an interaction between hormonal status and cognitive response to stress in female rats, with high estrogen levels being associated with amplified sensitivity to stress. This effect has been previously observed after administration of a pharmacological stressor (the benzodiazepine inverse agonist FG7142), and results from both studies may be relevant to the increased prevalence of stress-related disorders, such as major depressive disorder, in cycling women. Overall, the results show that restraint stress has important effects on the cognitive functions of the PFC, and that hormonal influences in the PFC are an important area for future research

A rationale and model for addressing tobacco dependence in substance abuse treatment

Most persons in drug treatment smoke cigarettes. Until drug treatment facilities systematically treat their patients' tobacco use, millions will flow through the drug treatment system, overcome their primary drug of abuse, but die prematurely from tobacco-related illnesses. This paper reviews the literature on the health benefits of quitting smoking for drug treatment patients, whether smoking causes relapse to other drug or alcohol abuse, the treatment of tobacco dependence, and good and bad times for quitting smoking among drug treatment patients. It also presents a conceptual model and recommendations for treating tobacco in substance abuse treatment, and provides references to internet and paper-copy tools and information for treating tobacco dependence. At present, research on tobacco treatment in drug treatment is in its infancy. Although few drug treatment programs currently offer formal services, many more will likely begin to treat nicotine dependence as external forces and patient demand for these services increases. In the absence of clear guidelines and attention to quality of care, drug treatment programs may adopt smoking cessation services based on cost, convenience, or selection criteria other than efficacy. Because research in this field is relatively new, substance abuse treatment professionals should adhere to the standards of care for the general population, but be prepared to update their practices with emerging interventions that have proven to be effective for patients in drug treatment