Mindfulness-based Group Intervention for an Adolescent Girl at Risk for Type 2 Diabetes: A Case Report.

CONTEXT: Behavioral lifestyle interventions to lower body mass index (BMI; kg/m2) are the standard approach for preventing adolescent-onset type 2 diabetes (T2D). Unfortunately, existing programs have had limited long-term success of lessening insulin resistance, the key physiological risk indicator for T2D. Underlying psychosocial factors, particularly depressive symptoms, have been related to insulin resistance, independent of BMI or body fat. Preliminary evidence indicates that mindfulness-based programs show promise for intervening with depression and T2D; yet, this approach is novel and data in adolescents are scarce. OBJECTIVE: The objectives of this study were (1) to evaluate the benefits, and potential underlying mechanisms, of a mindfulness-based intervention in adolescents at-risk for T2D with depressive symptoms and (2) to consider clinical implementation with this specific, psychologically, and medically at-risk adolescent population. DESIGN AND SETTING: The research team conducted a case study report. The setting was an outpatient therapy clinic and research laboratory at a university. PARTICIPANT: The participant was a 16-y-old female with elevated depressive symptoms, obesity, and insulin resistance, and a family history of T2D. INTERVENTION AND OUTCOMES: The intervention was a 6-wk mindfulness-based group program. The key outcomes were patterns of change in trait mindfulness, depression, and insulin resistance in the course of a 1-y follow-up. Secondary outcomes were patterns of change in reported-overeating patterns and cortisol awakening response. RESULTS: Compared with her scores at baseline, the participant displayed a pattern of increased trait mindfulness, decreased depressive symptoms, and lessening of insulin resistance immediately following the group program and at 1 y. BMI and body fat were stable. There was a remission in reported-overeating and a pattern of declining cortisol awakening response 1 y later. Participant feedback on the intervention was generally positive but also provided potential modifications to strengthen acceptability and effectiveness. CONCLUSIONS: The current case results suggest that teaching mindfulness skills to adolescent girls at risk for T2D with depressive symptoms may offer distinctive advantages for treating depression and T2D risk. Clinical implications for increasing the success of implementing mindfulness-based programs in this population include a focus on promotion of social connectedness within the group, implementation of strategies to increase adherence to home practice activities, and the use of facilitation techniques to promote concrete understanding of abstract mindfulness concepts. Future, adequately powered clinical trial data are required to test therapeutic mechanisms and recommended adaptations.

Learning to BREATHE: an intervention to foster mindfulness in adolescence.

During adolescence, young people are traversing exciting and also challenging stages in their development. Mindfulness, if taught in a developmentally appropriate way, has the potential to be an asset in adolescents' lives. Developmentally appropriate approaches of mindfulness intervention during adolescence need to consider adolescents' social contexts (for example, school setting, peer group, family), their cognitive and emotional stages in development, and age-specific strength and vulnerabilities. This chapter puts mindfulness education into a developmental perspective, and presents the Learning to BREATHE program as a school-based universal intervention for adolescents. The authors describe developmental dimensions and themes of the program, and discuss common challenges of program implementation in schools. A case example of bringing the Learning to BREATHE program into the school context is provided.

Mindfulness for adolescents: a promising approach to supporting emotion regulation and preventing risky behavior.

This article reviews the contextual and neuropsychological challenges of the adolescent period with particular attention to the role that universal prevention can play in moderating the harmful effects of stress. The centrality of emotion regulation skills to long-term health and wellness suggests their importance in prevention and intervention efforts for youth. Mindfulness has been shown to be an effective means of reducing stress and improving emotion balance in research with adults, although research on mindfulness with adolescents is limited. The authors present available data and describe one potentially effective program for adolescent mindfulness: Learning to BREATHE.

Biosensors for brain trauma and dual laser doppler flowmetry: enoxaparin simultaneously reduces stroke-induced dopamine and blood flow while enhancing serotonin and blood flow in motor neurons of brain, in vivo.

Neuromolecular Imaging (NMI) based on adsorptive electrochemistry, combined with Dual Laser Doppler Flowmetry (LDF) is presented herein to investigate the brain neurochemistry affected by enoxaparin (Lovenox(®)), an antiplatelet/antithrombotic medication for stroke victims. NMI with miniature biosensors enables neurotransmitter and neuropeptide (NT) imaging; each NT is imaged with a response time in milliseconds. A semiderivative electronic reduction circuit images several NT's selectively and separately within a response time of minutes. Spatial resolution of NMI biosensors is in the range of nanomicrons and electrochemically-induced current ranges are in pico- and nano-amperes. Simultaneously with NMI, the LDF technology presented herein operates on line by illuminating the living brain, in this example, in dorso-striatal neuroanatomic substrates via a laser sensor with low power laser light containing optical fiber light guides. NMI biotechnology with BRODERICK PROBE(®) biosensors has a distinct advantage over conventional electrochemical methodologies both in novelty of biosensor formulations and on-line imaging capabilities in the biosensor field. NMI with unique biocompatible biosensors precisely images NT in the body, blood and brain of animals and humans using characteristic experimentally derived half-wave potentials driven by oxidative electron transfer. Enoxaparin is a first line clinical treatment prescribed to halt the progression of acute ischemic stroke (AIS). In the present studies, BRODERICK PROBE(®) laurate biosensors and LDF laser sensors are placed in dorsal striatum (DStr) dopaminergic motor neurons in basal ganglia of brain in living animals; basal ganglia influence movement disorders such as those correlated with AIS. The purpose of these studies is to understand what is happening in brain neurochemistry and cerebral blood perfusion after causal AIS by middle cerebral artery occlusion in vivo as well as to understand consequent enoxaparin and reperfusion effects actually while enoxaparin is inhibiting blood clots to alleviate AIS symptomatology. This research is directly correlated with the medical and clinical needs of stroke victims. The data are clinically relevant, not only to movement dysfunction but also to the depressive mood that stroke patients often endure. These are the first studies to image brain neurotransmitters while any stroke medications, such as anti-platelet/anti-thrombotic and/or anti-glycoprotein are working in organ systems to alleviate the debilitating consequences of brain trauma and stroke/brain attacks.

Exploring Fidelity in School-Based Mindfulness Programs.

A small but growing body of research on school-based mindfulness programs (SBMPs) has demonstrated benefits for students' cognitive and affective functioning and overall wellbeing. Yet, lack of fidelity in SBMP implementation may diminish these programs' purported benefits. This commentary presents 4 current challenges that need to be addressed so that questions of whether and how mindfulness improves student functioning can be clarified and implementation of programs can be strengthened and sustained. These challenges include coming to consensus on the definition and intention of mindfulness training, balancing adherence with flexibility in SBMP delivery, determining the role SBMP teachers' mindfulness experience plays in program fidelity, and delineating distinctive features of mindful pedagogy. Some suggestions for addressing each of these challenges are provided.

A College First-Year Mindfulness Seminar to Enhance Psychological Well-Being and Cognitive Function.

Mindfulness training (MT) has shown promise in improving psychological health among college students, yet has rarely been evaluated as an addition to the college academic curriculum. Here, we demonstrate the feasibility and effectiveness of a first-year MT seminar offered to residential students at a selective private university, evaluating its impact on psychological and cognitive functioning, in relationship to a comparable positive psychology seminar. The results suggest the potential for first-year programs that promote student well-being.

Mindfulness Interventions to Reduce Impact of Interparental Conflict on Adolescents.

Exposure to frequent, intense, and poorly resolved interparental conflict puts adolescents at risk for problems in many domains, including internalizing and externalizing problems, and stress physiological dysfunction. Existing intervention strategies to target these adolescents focus almost solely on improving marital dynamics, for example, through relationship education or couples therapy. However, interventions that aim to enhance marital communication require high levels of parental commitment and motivation for change, and may be expensive and time-consuming. In the current paper, we argue that it is essential to also apply intervention strategies that directly promote the regulatory capabilities of adolescents to improve outcomes for youth from high-conflict homes. Mindfulness, or present-moment, nonjudgemental awareness, is associated with myriad positive outcomes in adults (e.g., lower levels of depression and anxiety, and greater emotion regulation). We propose that mindfulness interventions are an ideal intervention strategy for adolescents from high conflict homes. Mindfulness interventions may target the mechanisms whereby destructive marital interaction impacts youth, by providing distance between experiences and evaluations, training regulation of attention, and enhancing self-compassion and nonjudgement, as well as by enhancing relationships. We also provide an example of a specific intervention model designed to increase mindfulness in youth, Learning to Breathe (L2B).

Learning to BREATHE "Plus": A Multi-Modal Adaptive Supplement to an Evidence-Based Mindfulness Intervention for Adolescents.

Incorporating technological supplements into existing group mindfulness-based interventions (MBIs), particularly for use with adolescents, is an important next step in the implementation of MBIs. Yet there is little available content. Herein we present the development and content of a technological supplement for MBIs, which incorporates multiple technological elements to support (a) skill transfer from the group MBI to daily life, (b) the establishment of a formal mindfulness practice, and (c) the use of mindfulness during periods of high stress. A mixed-methods approach was used to develop this multi-method adaptive supplement. Findings about the use of this supplement will be disseminated scientifically and/or publicly as appropriate.

New Avenues for Promoting Mindfulness in Adolescence using mHealth.

There is a large evidence base supporting the efficacy of mindfulness interventions in adulthood, and growing support for the efficacy of these interventions in adolescence. Historically mindfulness interventions have been delivered in person and in groups, with recommendations for home practice being a critical part of the intervention. However, compliance with these practice recommendations in adolescence is very poor. Past studies indicate that using mobile technology to promote skill transfer to real life can be an effective strategy, particularly when used as a supplement to an in-person intervention strategy. To date, however, mobile technology has largely been used to create stand-alone mindfulness interventions. The goals of the current paper are to discuss the potential opportunities and challenges with a mobile-technology-enhanced mindfulness intervention, and to present the rationale that such an approach is not only theoretical and empirically sound but also a critical next step to increase the efficacy and developmental appropriateness of mindfulness interventions for adolescents. This discussion is grounded in a specific example of a mindfulness intervention supplemented by momentary interventions we are developing.

Moving 2 Mindful (M2M) study protocol: testing a mindfulness group plus ecological momentary intervention to decrease stress and anxiety in adolescents from high-conflict homes with a mixed-method longitudinal design.

INTRODUCTION: Interparental conflict exposure places adolescents at risk for problems with stress and anxiety; existing prevention/intervention strategies focus on reducing interparental conflict. Mindfulness-based programmes may be a promising treatment strategy for this population, but studies have not yet tested whether they are effective in this high-conflict context. In addition, evidence suggests that extensions to traditional treatments, such as delivering components in daily life that are tailored to moments of need, can increase treatment efficacy, particularly when combined with in-person treatments and particularly for adolescents. However, there are no such extensions to mindfulness interventions available. The Moving 2 Mindful study aims to (1) develop an ecological momentary intervention (EMI) supplement to Learning to BREATHE (L2B), an evidence-based mindfulness intervention for adolescents; (2) refine the EMI programme and determine the best delivery plan; (3) examine the feasibility and acceptability of L2B Plus (L2B plus the developed supplement) and (4) examine the potential for L2B Plus to reduce stress and anxiety for adolescents from high-conflict homes. METHODS AND ANALYSIS: The Moving 2 Mindful study proposes a mixed-methods approach to developing and refining a multimethod adaptive supplement to L2B. Feasibility, acceptability and potential effectiveness will be tested in a sample of 38 families, who will be randomly assigned to receive L2B Plus or an active health and wellness control condition and followed until 3 months postintervention. A range of psychosocial and physiological factors will be assessed at multiple time points. This study is registered with clinicaltrials.gov (ID NCT03869749; pre-results). ETHICS AND DISSEMINATION: The Institutional Review Board at Colorado State University has approved this study. Findings will be disseminated in scientific journals and conferences, whether they are positive, negative or inconclusive.

One-Year Follow-Up of a Randomized Controlled Trial Piloting a Mindfulness-Based Group Intervention for Adolescent Insulin Resistance.

INTRODUCTION: To explore if a brief mindfulness-based intervention (MBI) leads to sustained, improved clinical outcomes in adolescents at-risk for type 2 diabetes (T2D). METHODS: Participants were 12-17y girls with overweight/obesity, elevated depression symptoms, and T2D family history participating in a randomized, controlled pilot trial of a six-session MBI vs. cognitive-behavioral therapy (CBT) group. At baseline and 1-year, mindfulness, depression, insulin resistance (IR), and body composition were assessed with validated instruments. RESULTS: One-year retention was 71% (n = 12) in MBI; 81% (n = 13) in CBT. At 1-year, depression decreased (Cohen's d = 0.68) and IR decreased (d = 0.73) in adolescents randomized to MBI compared to those in CBT. There were no significant between-condition differences in mindfulness, adiposity, or BMI. DISCUSSION: One-year outcomes from this randomized, controlled pilot trial suggest that brief MBI may reduce depression and IR in at-risk adolescents. Replication and exploration of mechanisms within the context of a larger clinical trial are necessary. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, identifier NCT02218138.

Laurate Biosensors Image Brain Neurotransmitters In Vivo: Can an Antihypertensive Medication Alter Psychostimulant Behavior?

Neuromolecular Imaging (NMI) with novel biosensors enables the selective detection of neurotransmitters in vivo within seconds, on line and in real time. Biosensors remain in place for continuing studies over a period of months. This biotechnological advance is based on conventional electrochemistry; the biosensors detect neurotransmitters by electron transfer. Simply stated, biosensors adsorb electrons from each neurotransmitter at specific oxidation potentials; the current derived from electron transfer is proportional to neurotransmitter concentration. Selective electron transfer properties of these biosensors permit the imaging of neurotransmitters, metabolites and precursors. The novel BRODERICK PROBE® biosensors we have developed, differ in formulation and detection capabilities from biosensors/electrodes used in conventional electrochemistry/ voltammetry. In these studies, NMI, specifically, the BRODERICK PROBE® laurate biosensor images neurotransmitter signals within mesolimbic neuronal terminals, nucleus accumbens (NAc); dopamine (DA), serotonin (5-HT), homovanillic acid (HVA) and Ltryptophan (L-TP) are selectively imaged. Simultaneously, we use infrared photobeams to monitor open-field movement behaviors on line with NMI in the same animal subjects. The goals are to investigate integrated neurochemical and behavioral effects of cocaine and caffeine alone and co-administered and further, to use ketanserin to decipher receptor profiles for these psychostimulants, alone and co-administered. The rationale for selecting this medication is: ketanserin (a) is an antihypertensive and cocaine and caffeine produce hypertension and (b) acts at 5-HT2A/2C receptors, prevalent in NAc and implicated in hypertension and cocaine addiction. Key findings are: (a) the moderate dose of caffeine simultaneously potentiates cocaine's neurochemical and behavioral responses. (b) ketanserin simultaneously inhibits cocaine-increased DA and 5-HT release in NAc and open-field behaviors and (c) ketanserin inhibits 5-HT release in NAc and open-field behaviors produced by caffeine, but, surprisingly, acts to increase DA release in NAc. Importantly, the latter effect may be a possible adverse effect of the moderate dose of caffeine in hypertensive patients. Thus, an antihypertensive medication is shown here to play a role in inhibiting brain reward possibly via antihypertensive mechanisms at DA and 5-HT receptor subtypes within DA motor neurons. An explanatory note for the results obtained, is the role likely played by the G Protein Receptor Complex (GPRC) family of proteins. Empirical evidence shows that GPRC dimers, heteromers and heterotrimers may cause cross-talk between distinct signalling cascade pathways in the actions of cocaine and caffeine. Ligand-directed functional selectivity, particularly for ketanserin, in addition to GPRCs, may also cause differential responses. The results promise new therapeutic strategies for drug addiction, brain reward and cardiovascular medicine.

Promoting healthy transition to college through mindfulness training with first-year college students: Pilot randomized controlled trial.

OBJECTIVE: Given the importance of developmental transitions on young adults' lives and the high rates of mental health issues among U.S. college students, first-year college students can be particularly vulnerable to stress and adversity. This pilot study evaluated the effectiveness and feasibility of mindfulness training aiming to promote first-year college students' health and wellbeing. PARTICIPANTS: 109 freshmen were recruited from residential halls (50% Caucasian, 66% female). Data collection was completed in November 2014. METHODS: A randomized control trial was conducted utilizing the Learning to BREATHE (L2B) program, a universal mindfulness program adapted to match the developmental tasks of college transition. RESULTS: Participation in the pilot intervention was associated with significant increase in students' life satisfaction, and significant decrease in depression and anxiety. Marginally significant decrease was found for sleep issues and alcohol consequences. CONCLUSIONS: Mindfulness-based programs may be an effective strategy to enhance a healthy transition into college.

Pilot randomized controlled trial of a mindfulness-based group intervention in adolescent girls at risk for type 2 diabetes with depressive symptoms.

OBJECTIVE: (1) Evaluate feasibility and acceptability of a mindfulness-based group in adolescent girls at-risk for type 2 diabetes (T2D) with depressive symptoms, and (2) compare efficacy of a mindfulness-based versus cognitive-behavioral group for decreasing depressive symptoms and improving insulin resistance. DESIGN AND SETTING: Parallel-group, randomized controlled pilot trial conducted at a university. PARTICIPANTS: Thirty-three girls 12-17y with overweight/obesity, family history of diabetes, and elevated depressive symptoms were randomized to a six-week mindfulness-based (n=17) or cognitive-behavioral program (n=16). INTERVENTIONS: Both interventions included six, one-hour weekly group sessions. The mindfulness-based program included guided mindfulness awareness practices. The cognitive-behavioral program involved cognitive restructuring and behavioral activation. MAIN OUTCOME MEASURES: Adolescents were evaluated at baseline, post-intervention, and six-months. Feasibility/acceptability were measured by attendance and program ratings. Depressive symptoms were assessed by validated survey. Insulin resistance was determined from fasting insulin and glucose, and dual energy x-ray absorptiometry was used to assess body composition. RESULTS: Most adolescents attended ≥80% sessions (mindfulness: 92% versus cognitive-behavioral: 87%, p=1.00). Acceptability ratings were strong. At post-treatment and six-months, adolescents in the mindfulness condition had greater decreases in depressive symptoms than adolescents in the cognitive-behavioral condition (ps<.05). Compared to the cognitive-behavioral condition, adolescents in the mindfulness-based intervention also had greater decreases in insulin resistance and fasting insulin at post-treatment, adjusting for fat mass and other covariates (ps<.05). CONCLUSIONS: A mindfulness-based intervention shows feasibility and acceptability in girls at-risk for T2D with depressive symptoms. Compared to a cognitive-behavioral program, after the intervention, adolescents who received mindfulness showed greater reductions in depressive symptoms and better insulin resistance. ClinicalTrials.gov identifier: NCT02218138 clinicaltrials.gov.

Monoamine and motor responses to cocaine are co-deficient in the Fawn-Hooded depressed animal model.

The Fawn-Hooded (FH) genetic animal model of depression continues to be of interest because the FH model has limited biochemical and immune function. The FH animal has an inherited trait, platelet storage pool deficiency (PSPD), an hemorrhagic disorder that is also a component of Chediak-Higashi syndrome (CHS). CHS is a pyrogenic infectious childhood disease; few patients live past the age of 20. Our hypothesis was that FH animals may exhibit different monoamine and motor responses to cocaine versus the Sprague-Dawley (SD) "normal" animal strain, which does not have the FH trait. Therefore, selective neuromolecular imaging (NMI) of the monoamines, dopamine (DA) and 5-HT within nucleus accumbens (NAcc) of behaving male FH versus SD rats was performed in vivo with BRODERICK PROBE sensors and a semiderivative voltammetric circuit. Each animal was placed in a faraday chamber and electrochemical signals were detected via a mercury commutator and flexible cable. Baseline values for neurotransmitters and behavior were derived during the last half-hour of habituation behavior. Release of DA and 5-HT was detected selectively, at separate oxidation potentials, within seconds, before and after intraperitoneal administration of the psychostimulant, cocaine (10 mg/kg). At the same time, frequencies of ambulations and central ambulations were separately monitored with infrared photobeams, which surrounded the faraday chamber. Data were compared by ANOVA analysis followed by Tukey's post hoc test. The data showed that (1) DA release in NAcc of behaving FH animals did not respond to cocaine; neither first hour nor second hour values significantly differed from baseline (both hours, p>0.05), whereas SD animals exhibited a significant increase in cocaine-induced DA release in NAcc (both hours, p<0.001). The ability for acute cocaine to increase DA release in NAcc was significantly greater in SD than in FH animals (p<0.001). (2) 5-HT release in NAcc of behaving FH animals was not significantly increased by cocaine (both hours, p>0.05), whereas 5-HT release in NAcc of SD animals was significantly increased after cocaine (both hours, p<0.001). The ability for acute cocaine to increase 5-HT release was significantly greater in SD than in FH animals (p<0.001). (3) Ambulations in the FH strain were modestly, yet significantly, enhanced after cocaine during both hours of study (p<0.05, p<0.001, respectively) as were ambulations in the SD strain. Nonetheless, the ability for acute cocaine to increase ambulations was significantly greater in SD than in FH animals in the first hour (p<0.001). (4) Central ambulations in the FH strain was not affected by cocaine (both hours, p>0.05), whereas SD animals showed a significant increase in central ambulatory activity in both hours of the cocaine study (p<0.001). The ability for acute cocaine to increase central ambulations was significantly greater in SD than in FH animals (p<0.001). Thus, this is the first study to determine in vivo the neurochemical response to acute cocaine in the behaving FH animal. Moreover, this is the first study to determine in vivo and simultaneously the neurochemical and behavioral response to acute cocaine in the FH strain in comparison with SD animals, a "normal" strain. Remarkable deficiencies in the ability for acute cocaine to alter neurochemistry and behavior in animals with the FH trait are shown. These studies emphasize the need to look differentially at cocaine effects in biochemically and immune-compromised subjects versus "normal" subjects.

Cytokines, stressors, and clinical depression: augmented adaptation responses underlie depression pathogenesis.

By influencing the central nervous system, cytokines, which regulate immune function innately and adaptively, may play a key role in mediating depression-like neuro-behavioral changes. However, the similarity between cytokine and stressor-effects in animal models raises a question about the degree to which behavioral and neurochemical outcomes of cytokine challenge represent depressive disorder per se. The present review attempts to illustrate the degree of overlap between cytokines and stressors with respect to their effects on neurochemistry and behavior in animal models. The review also shows how short-term effects of cytokine exposure in typical animals may be discerned from characteristics that might otherwise be described as depression-like. By comparing outcomes of immune challenge in typical rodent strains (e.g., Sprague-Dawley [SD], Wistar) and an accepted animal model of depression (e.g., Fawn Hooded [FH] rodent strain), differences between short-term effects of cytokines and depression-like characteristics in rodents are demonstrated. Additionally, because it is known that preexisting vulnerability to depression may affect outcomes of immune challenge, we further compare immunological, biochemical and behavioral effects of cytokines between SD and FH rodent strains. Interestingly, the acute neurochemical and behavioral effects of the cytokine interleukin 1alpha (IL-1alpha) reveal stressor-like responses during behavioral habituation in both strains, though this appears to a stronger degree in FH animals. Further, the subacute response to IL-1alpha vastly differed between strains, indicating differences in adaptive mechanisms. Thus, stressor-like effects of immune challenge, particularly in FH animals, provide validation for recent "cross-sensitization" models of depression pathogenesis that incorporate immune factors.

Interleukin 1alpha alters hippocampal serotonin and norepinephrine release during open-field behavior in Sprague-Dawley animals: differences from the Fawn-Hooded animal model of depression.

Detection of two biogenic amine neurotransmitters, serotonin (5-HT) and norepinephrine (NE) within the CA1 region of the hippocampus (HPC) of behaving male laboratory animals (Rattus norvegicus), was performed with miniature carbon sensors (BRODERICK PROBES) and in vivo semidifferential microvoltammetry after acute administration of the soluble immune factor, human recombinant, interleukin (IL) 1alpha (10 and 100 ng/kg i.p.). Two animal models were compared, i.e., (a) the Sprague-Dawley (SD) model, a strain neither biochemically nor immune-challenged and (b) the Fawn-Hooded (FH) model, a biochemically (5-HT-deficient) and immune-challenged animal. Open-field behaviors, locomotion (ambulations) and stereotypy (fine movements of sniffing and grooming) were monitored with infrared photobeams while 5-HT and NE were selectively and separately detected within seconds in real time. Subchronic studies were performed in the same animals 24 h later at which time no further drug was administered. Results from acute treatment studies showed that IL-1alpha altered HPC monoamines and behavior viz-a-viz habituation values (baseline) in the SD strain differently from those in the FH strain as follows: (1) although 5-HT release was significantly increased within CA1 region of HPC in both SD and FH strains (P<.0001), the extent of the HPC 5-HT increase in the 5-HT-deficient FH strain was significantly less than that of the SD strain at both doses (P<.0001). The subchronic studies showed that 5-HT release within the HPC in the SD strain significantly increased (135%) over drug treatment values (P<.001), whereas HPC 5-HT release in the FH strain remained the same as that seen in the acute drug treatment studies; the difference between strains for the subchronic study was also statistically significant (P<.01). (2) IL-1alpha significantly decreased HPC NE release in the SD strain (P<.0004) while IL-1alpha decreased HPC NE release in the FH strain only at the 10-ng/kg dose (P<.001); at the 100-ng/kg dose in the FH strain, NE rebounded towards baseline and increased 15% above baseline reaching statistical significance (P<.05). Subchronic studies in the SD strain showed a further decreased NE signal to 38% below baseline (P<.0001), whereas subchronic studies in the FH strain showed a significant increase in NE release (P<.02). The difference between strains in the subchronic NE studies was significant (P<.001). (3) Ambulations were increased after IL-1alpha administration in acute studies in both the SD and the FH strains, but the increase did not reach statistical significance, whereas in the subchronic studies, both strains exhibited significant increases as revealed by post hoc analyses (P<.05). There was a statistically significant difference between strains in acute studies (P<.001), whereas no significant differences between models were seen in ambulation behavior in subchronic studies. (4) Fine movements increased over baseline after IL-1alpha administration in both animal models in acute studies, however, results did not reach statistical significance, likely due to the episodic effect of IL-1alpha on movement behavior in both the SD and the FH strains. However, the SD strain showed a significant increase in fine movement behavior during the subchronic studies (P<.02). Significant differences in fine movements between animal models were not observed either acutely or in subchronic studies. In summary, the data show that immune modulation by IL-1alpha affects HPC neurochemistry and behavior in SD versus FH animal models differently and/or to different degrees. The data show that while the FH animal model is subsensitive to 5-HT agonists, 5-HT function can be stimulated. Comparison of genetically diverse animal models provides a reliable means to identify and discern cytokine-induced depressive versus stressor properties. Selective sensor technology provides a powerful tool as movement behavior is monitored and interpreted as a function of monoamine neurotransmission.

Acute and subacute effects of risperidone and cocaine on accumbens dopamine and serotonin release using in vivo microvoltammetry on line with open-field behavior.

In vivo microvoltammetry was used to detect dopamine (DA) and serotonin (5-HT) release from nucleus accumbens (NAcc) of freely moving, male, Sprague-Dawley laboratory rats, while animals' locomotor (forward ambulations) and stereotypic behavior (fine movements of sniffing and grooming) were monitored at the same time with infrared photobeams. Monoamine release mechanisms were determined by using a depolarization blocker (gamma-butyrolactone, gamma BL). Miniature carbon sensors (BRODERICK PROBES microelectrodes) smaller than a human hair were used in conjunction with a semidifferential electrochemical circuit to detect release of each monoamine in separate signals and within seconds. The purpose was to evaluate the neuropharmacology of the 5-HT(2)/DA(2) antagonist risperidone in its current therapeutic role as an atypical antipsychotic medication as well as in its potential role as pharmacotherapy for cocaine psychosis and withdrawal symptoms. Acute (single drug dose) and subacute (24-h follow-up studies in the same animal, no drug administration) studies were performed for each treatment group. The hypothesis for the present studies is derived from a growing body of evidence that cocaine-induced psychosis and schizophrenic psychosis share similar neurochemical and behavioral manifestations. Results showed that (1) Acute administration of risperidone (2 mg/kg sc) significantly increased DA and 5-HT release in NAcc above baseline (habituation) values (P<.001) while locomotion and stereotypy were virtually unaffected. In subacute studies, DA release did not differ from baseline (P>.05), whereas 5-HT release was significantly increased above baseline (P<.001). Locomotion increased over baseline but not to a significant degree, while stereotypy was significantly increased above baseline (P<.05). (2) Acute administration of cocaine (10 mg/kg ip) significantly increased both DA and 5-HT release above baseline (P<.001), while locomotion and stereotypy were significantly increased over baseline (P<.001). In subacute studies, DA decreased significantly below baseline (P<.001) and significant decreases in 5-HT release occurred at 15, 20, 50 and 55 min (P<.05). Behavior increased above baseline but did not reach a statistically significant degree. (3) Acute administration of risperidone/cocaine (2 mg/kg sc and 10 mg/kg ip, respectively) showed a significant block of the cocaine-induced increase in DA release in the first hour (P<.001) and 5-HT release in both hours of study (P<.001). Cocaine-induced locomotion and stereotypy were blocked simultaneously with the monoamines (P<.001). In subacute studies, DA and 5-HT release returned to baseline while locomotion and stereotypy increased insignificantly above baseline. Thus, (a) these studies were able to tease out pharmacologically the critical differences between presynaptic and postsynaptic responses to drug treatment(s) and these differences may lead to more effective therapies for schizophrenic and/or cocaine psychosis. (b) Taken together with other data, these acute studies suggest that risperidone may possibly act via inhibition of presynaptic autoreceptors to produce the observed increases in accumbens DA and 5-HT release, whereas cocaine may be acting at least in part via serotoninergic modulation of DA postsynaptically. The subacute data suggest that pharmacokinetics may play a role in risperidone's action and that neuroadaptation may play a role in the mechanism of action of cocaine. Finally, the ability of risperidone to block cocaine-induced psychostimulant neurochemistry and behavior during acute studies while diminishing the withdrawal symptoms of cocaine during subacute studies suggests that risperidone may be a viable pharmacotherapy for cocaine psychosis and withdrawal.