Mesolimbic Tract Research Articles

Aging of reward dopamine tracts in the human brain: A diffusion tensor imaging study.

The mesocortical tract (MCT) and mesolimbic tract (MLT) are reward dopaminergic tracts that have been shown to play a role in regulating reward stimuli, including both incentive salience and social stimuli. In the current study, we examined aging of the MCT and MLT in normal human participants to explain human brain structures using diffusion tensor tractography (DTT). Sixty-four healthy participants were recruited for this study and allocated to 3 groups based on participants' age. Diffusion tensor imaging was performed, and MCTs and MLTs were reconstructed using the probabilistic tractography method. A significant negative correlation was observed between age and fractional anisotropy and tract volume of the MCT and MLT, whereas a positive correlation was observed between age and mean diffusivity. The mean fractional anisotropy value of the MCT was significantly lower in the old group than in the young and middle-aged groups (P < .05). The mean diffusivity values of the MCT and MLT were significantly higher in the old group than in the young and middle-aged groups (P < .05). The mean tract volume values of the MCT and MLT were significantly lower in the old group than in the young group (P < .05). We found that degenerative changes in the MCT and MLT began in participants in the 20s-30s, progressed steadily throughout life, and accelerated in the 60s.

Neural Injury of the Dopaminergic Pathways in Patients with Middle Cerebral Artery Territory Infarct: A Diffusion Tensor Imaging Study

The mesocortical tract (MCT) and mesolimbic tract (MLT), dopaminergic pathways originating from the ventral tegmental area in the midbrain to the ventral striatum (nucleus accumbens) and prefrontal cortex, play a crucial role in regulating incentive salience. This study aimed to investigate the potential changes in the MCT and MLT pathways following ischemic stroke, such as middle cerebral artery (MCA) infarction. We enrolled thirty-six patients with MCA infarction and forty healthy individuals with no history of psychiatric or neurological disorders. Using diffusion tensor tractography, we examined the injury to the affected and unaffected MCT and MLT pathways in patients with MCA infarction, comparing them to the control group. Our findings revealed a significant difference in the mean values of fractional anisotropy (FA) and tract volume (TV) of the MCT and MLT pathways between the patient and control groups (p &lt; 0.05). Specifically, the mean FA of the MCT and MLT showed a decrease of 7.94% and 6.33%, respectively, in the affected side compared to the control group (p &lt; 0.05). Similarly, the mean TV of the MCT and MLT showed a decrease of 73.22% and 78.79%, respectively, in the affected side compared to the control group (p &lt; 0.05). These changes were significantly different from those of the unaffected MCT, MLT, and control groups (p &lt; 0.05). Our study suggests that MCA infarction can cause significant damage to the affected MCT and MLT pathways, potentially contributing to our understanding of the pathophysiology of post-stroke depression.

Aging of the mesolimbic tract in the human brain: A diffusion tensor imaging study.

The mesolibic tract (MLT) is a dopaminergic tract that has been shown to play a role in regulating reward stimuli, including both incentive salience and social stimuli. In the current study, we examined the aging of MLT in normal human participants to explain human brain structures using diffusion tensor tractography (DTT). Fifty-seven healthy participants were recruited for this study and allocated to six groups based on their age. Diffusion tensor imaging (DTI) scanning was performed and MLTs were reconstructed using the probabilistic tractography method. MLTs were defined by selecting fibers passing through the seed and target regions of interest placed on the ventral segmental area and nucleus accumbens. A significant negative correlation was observed between age and the voxel number (VN) of MLT, while a positive correlation was observed between age and the apparent diffusion coefficient (ADC). The mean VN value of the MLT was significantly lower in the 60s and 70s age groups than in the 20s, 40s, and 50s (P < .05). The mean ADC value of the MLT was significantly higher in the 60s and 70s groups than in the 20s, 30s, and 40s, 50s groups (P < .05). We found that aging of the MLT began in the 20s or 30s and progressed steadily throughout life until the 60s, when it exhibited significant degeneration. We believe this affect may play a role in the decline of memory and social interaction with aging in normal participants.

Dopamine antagonist antipsychotics in diverted forensic populations.

In community settings, negative symptoms and cognitive deficits are the primary barriers to independent living, stable relationships, and employment for individuals suffering from schizophrenia-spectrum disorders. In contrast, however, positive psychotic symptoms (e.g., command hallucinations and persecutory delusions) often drive behavior which serves as the gateway to arrest and criminalization. Historically, the keystone of treatment for positive psychotic symptoms has been antagonism of dopamine D2 receptors in the mesolimbic tract. In this article, we review and explore the principles underlying dopamine antagonism for the treatment of psychosis; optimization of dopamine antagonists in treating positive psychotic symptoms; the advantages of depot dopamine antagonist antipsychotics in forensic settings; the concepts of pharmacokinetic and pharmacodynamic treatment failures; and the role of medication plasma concentrations in optimizing and managing treatment.

Review of Clinical Handbook of Psychotropic Drugs for Children and Adolescents, 3rd Ed., edited by Dean Elbe, Kalyna Z. Bezchlibnyk-Butler, Adil S. Virani, and Ric M. Procyshyn

[Author Affiliation]Malgorzata Maria Relja. 1 Department of Psychiatry, Dalhousie University, Fredericton, New Brunswick, Canada.Mira Sachdev. 2 A4 - Private Practice, Titusville, Florida.ISBN: 0.88937.456.2. Boston, MA, Hogrefe Publishing, 2014, 362 pages.Address Correspondence to: Malgorzata Maria Relja, MD, Department of Psychiatry, Dalhousie University, 65 Brunswick Street, Fredericton, NB E3B 1G5, Canada, E-mail: margaret.relja@gnb.caMira Sachdev, MD, Private Practice, 860 Century Medical Drive, Titusville, FL 32796, E-mail: mira.sachdev@gmail.comFor most child and adolescent psychiatrists, psychopharmacology is challenging because of the need to stay current while new information is constantly added. Psychotropic medications are powerful agents that treat many disorders, but also can impose a great risk if not used accordingly. We need to keep dry minutiae in our knowledge base and, therefore, there is a great value of a book to serve as a practical resource guide to quickly access relevant information.Dean Elbe, PharmD, a Canadian clinical pharmacist specialist at British Columbia Children's Hospital and colleagues have written a user-friendly book about prescribing psychotropic medications for children and adolescents. This handbook contains prescribing information for the United States and Canada. It fills a void for Canadian practitioners since most other psychopharmacology books readily available in North America only contain prescribing information for the United States. This book is targeted toward multiple disciplines, including child and adolescent psychiatrists, pediatricians, and nurses. Also this book acknowledges indications for adults and is suitable as an adult reference. FDA-approved indications for children and adolescents are emphasized, but nonapproved indications are also included.This book makes dry material more interesting and is pleasing to the eye. There are several things that make this book different from other psychopharmacology resources as opposed to an online reference. As it is spiral bound with text written in landscape format, it is easy to lay the book flat and read both pages at once. As a book, it can be left open on the table; it does not require toggling between screens as with a computerized medical record. Thus, it is easy to highlight and make notations on paper. There are online resources available, but they do not have the easy digestibility of this color-coded volume.The majority of the book is organized into chapters per class of drugs, such as chapters on antidepressants, antipsychotics, mood stabilizers, anxiolytics, hypnotics/sedatives, and drugs for attention-deficit/hyperactivity disorder (ADHD). There are chapters dedicated to drugs/substances of abuse and its substance abuse treatment, electroconvulsive therapy, unapproved treatments of psychiatric disorders, and natural health products. In each chapter there are color-coded sections such as Indications, Dosing, Pharmacokinetics, Switching Formulations, Adverse Effects, Discontinuation Syndrome, Contraindications, Toxicity, Monitoring, Use in Pregnancy, and Nursing Implications. There is also a set of caregiver information sheets available online.Many of the chapters function as review articles about a class of medications. Basic psychopharmacology is covered well. For example, the chapter on antipsychotics contained an excellent clinical description of dopaminergic rebound in two sentences. If a high D2 affinity medication (e.g., risperidone) is abruptly replaced with a low D2 affinity medication or a rapid on/off fast-dissociating antipsychotic (e.g., quetiapine) or a partial D2 agonist (e.g., aripiprazole), dopaminergic rebound may result. In the mesolimbic tract, this could lead to supersensitivity psychosis; in the nigrostriatal tract, treatment-emergent EPS and TD may materialize (p. 194).The many tables in each chapter are one of the best features. …

Moderate voluntary exercise attenuates the metabolic syndrome in melanocortin-4 receptor-deficient rats showing central dopaminergic dysregulation.

ObjectiveMelanocortin-4 receptors (MC4Rs) are highly expressed by dopamine-secreting neurons of the mesolimbic tract, but their functional role has not been fully resolved. Voluntary wheel running (VWR) induces adaptations in the mesolimbic dopamine system and has a myriad of long-term beneficial effects on health. In the present experiments we asked whether MC4R function regulates the effects of VWR, and whether VWR ameliorates MC4R-associated symptoms of the metabolic syndrome.MethodsElectrically evoked dopamine release was measured in slice preparations from sedentary wild-type and MC4R-deficient Mc4rK314X (HOM) rats. VWR was assessed in wild-type and HOM rats, and in MC4R-deficient loxTBMc4r mice, wild-type mice body weight-matched to loxTBMc4r mice, and wild-type mice with intracerebroventricular administration of the MC4R antagonist SHU9119. Mesolimbic dopamine system function (gene/protein expression) and metabolic parameters were examined in wheel-running and sedentary wild-type and HOM rats.ResultsSedentary obese HOM rats had increased electrically evoked dopamine release in several ventral tegmental area (VTA) projection sites compared to wild-type controls. MC4R loss-of-function decreased VWR, and this was partially independent of body weight. HOM wheel-runners had attenuated markers of intracellular D1-type dopamine receptor signaling despite increased dopamine flux in the VTA. VWR increased and decreased ΔFosB levels in the nucleus accumbens (NAc) of wild-type and HOM runners, respectively. VWR improved metabolic parameters in wild-type wheel-runners. Finally, moderate voluntary exercise corrected many aspects of the metabolic syndrome in HOM runners.ConclusionsCentral dopamine dysregulation during VWR reinforces the link between MC4R function and molecular and behavioral responding to rewards. The data also suggest that exercise can be a successful lifestyle intervention in MC4R-haploinsufficient individuals despite reduced positive reinforcement during exercise training.

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Hirsutism in a Female Adolescent Induced by Long-Acting Injectable Risperidone

Dopamine and serotonin: influences on male sexual behavior

Steroid hormones regulate sexual behavior primarily by slow, genomically mediated effects. These effects are realized, in part, by enhancing the processing of relevant sensory stimuli, altering the synthesis, release, and/or receptors for neurotransmitters in integrative areas, and increasing the responsiveness of appropriate motor outputs. Dopamine has facilitative effects on sexual motivation, copulatory proficiency, and genital reflexes. Dopamine in the nigrostriatal tract influences motor activity; in the mesolimbic tract it activates numerous motivated behaviors, including copulation; in the medial preoptic area (MPOA) it controls genital reflexes, copulatory patterns, and specifically sexual motivation. Testosterone increases nitric oxide synthase in the MPOA; nitric oxide increases basal and female-stimulated dopamine release, which in turn facilitates copulation and genital reflexes. Serotonin (5-HT) is primarily inhibitory, although stimulation of 5-HT2C receptors increases erections and inhibits ejaculation, whereas stimulation of 5-HT1A receptors has the opposite effects: facilitation of ejaculation and, in some circumstances, inhibition of erection. 5-HT is released in the anterior lateral hypothalamus at the time of ejaculation. Microinjections of selective serotonin reuptake inhibitors there delay the onset of copulation and delay ejaculation after copulation begins. One means for this inhibition is a decrease in dopamine release in the mesolimbic tract.

Mesostriatal and mesolimbic dopamine uptake binding sites are reduced in Parkinson's disease and progressive supranuclear palsy: A quantitative autoradiographic study using [ 3H]mazindol

It has been suggested that not only mesostriatal but also mesolimbic pathways are involved in the degeneration of dopaminergic neurons in Parkinson's disease. Using quantitative ligand autoradiography we have investigated dopamine transporter sites in basal ganglia of patients affected by Huntington's chorea, Parkinson's disease and progressive supranuclear palsy. [ 3H]Mazindol, a ligand for catecholamine uptake, was used in the presence of desipramine to block the binding to norepinephrine uptake sites. Schizophrenic cases were entered in the study to take into account the effects of neuroleptics, commonly administered also to Huntington's disease patients, on dopamine uptake sites. In control cases high densities of [ 3H]mazindol binding sites were found in the caudate nucleus, putamen and nucleus accumbens, whereas very low densities were present in substantia nigra and ventral tegmental area. In Huntington's chorea the density of [ 3H]mazindol binding sites was slightly decreased in the caudate nucleus, an area severely affected by the neurodegenerative process. In schizophrenic patients the density of dopamine uptake sites in the basal ganglia was slightly reduced, mainly in the middle third of putamen. Both Parkinson's disease and progressive supranuclear palsy populations were characterized by a marked loss of [ 3H]mazindol binding sites in the neostriatum (about 75%) and in the nucleus accumbens (about 65%). These results suggest that in Parkinson's disease and progressive supranuclear palsy severe decreases of dopamine uptake sites occur not only in the mesostriatal pathway but also in the mesolimbic tract.