Optogenetic Interrogation of Dopaminergic Modulation of the Multiple Phases of Reward-Seeking Behavior

Journal of Neuroscience, Journal Year: 2011, Volume and Issue: 31(30), P. 10829 - 10835

Published: July 27, 2011

Phasic activation of dopaminergic neurons is associated with reward-predicting cues and supports learning during behavioral adaptation. While noncontingent in the ventral tegmental are (VTA) sufficient for passive conditioning, it remains unknown whether phasic signal truly reinforcing. In this study, we first targeted expression channelrhodopsin-2 to VTA optimized optogenetically evoked dopamine transients. Second, showed that freely moving mice causally enhances positive reinforcing actions a food-seeking operant task. Interestingly, such effect was not found absence food reward. We further reactivate previously extinguished behavior external cues. This also confirmed using single-session reversal paradigm. Collectively, these data suggest facilitates development reinforcement reward-seeking flexibility.

Language: Английский

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Cannabis Use and Risk of Psychiatric Disorders

JAMA Psychiatry, Journal Year: 2016, Volume and Issue: 73(4), P. 388 - 388

Published: Feb. 17, 2016

With rising rates of marijuana use in the general population and an increasing number states legalizing recreational authorizing medical programs, there are renewed clinical policy concerns regarding mental health effects cannabis use.To examine prospective associations between risk substance disorders adult population.A nationally representative sample US adults aged 18 years or older was interviewed 3 apart National Epidemiologic Survey on Alcohol Related Conditions (wave 1, 2001-2002; wave 2, 2004-2005). The primary analyses were limited to 34 653 respondents who both waves. Data analysis conducted from March 15 November 30, 2015.We used multiple regression propensity score matching estimate strength independent at 1 incident prevalent psychiatric 2. Psychiatric measured with a structured interview (Alcohol Use Disorder Associated Disabilities Interview Schedule-DSM-IV). In analyses, same set confounders used, including sociodemographic characteristics, family history disorder, disturbed environment, childhood parental loss, low self-esteem, social deviance, education, recent trauma, past present disorders, respondent's divorce.In (14 564 male [47.9% weighted]; mean [SD] age, 45.1 [17.3] years), (2001-2002), which reported by 1279 respondents, significantly associated 2 (2004-2005) (any disorder: odds ratio [OR], 6.2; 95% CI, 4.1-9.4; any alcohol OR, 2.7; 1.9-3.8; 9.5; 6.4-14.1; other drug 2.6; 1.6-4.4; nicotine dependence: 1.7; 1.2-2.4), but not mood disorder (OR, 1.1; 0.8-1.4) anxiety 0.9; 0.7-1.1). pattern results observed score-matched disorders.Within population, is increased for several disorders. Physicians makers should take these under careful consideration.

Language: Английский

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The Dopamine Hypothesis of Drug Addiction and Its Potential Therapeutic Value

Frontiers in Psychiatry, Journal Year: 2011, Volume and Issue: 2

Published: Jan. 1, 2011

Dopamine (DA) transmission is deeply affected by drugs of abuse, and alterations in DA function are involved the various phases drug addiction potentially exploitable therapeutically. In particular, basic studies have documented a reduction electrophysiological activity neurons alcohol, opiate, cannabinoid, other drug-dependent rats. Further, release Nucleus accumbens (Nacc) decreased virtually all rodents. parallel, these supported increments intracranial self stimulation (ICSS) thresholds during withdrawal from nicotine, opiates, thereby suggesting hypofunction neural substrate ICSS. Accordingly, morphological evaluations fed into realistic computational analysis medium spiny neuron Nacc, post-synaptic counterpart terminals, show profound changes structure entire mesolimbic system. line with findings, human imaging shown dopamine receptors accompanied lesser endogenous ventral striatum cocaine, heroin, alcohol-dependent subjects, offering visual proof "dopamine-impoverished" addicted brain. The lasting physiological system leads to idea that an increment its activity, restore pre-drug levels, may yield significant clinical improvements (reduction craving, relapse, drug-seeking/taking). theory, it be achieved pharmacologically and/or novel interventions such as transcranial magnetic (TMS). Its anatomo-physiological rationale possible therapeutic aid alcoholics addicts will described proposed theoretical framework subjected experimental testing addicts.

Language: Английский

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Risky Decision Making, Prefrontal Cortex, and Mesocorticolimbic Functional Connectivity in Methamphetamine Dependence

JAMA Psychiatry, Journal Year: 2014, Volume and Issue: 71(7), P. 812 - 812

Published: May 21, 2014

Various neuropsychiatric disorders, especially addictions, feature impairments in risky decision making; clarifying the neural mechanisms underlying this problem can inform treatment.To determine how methamphetamine-dependent and control participants differ brain activation during a decision-making task, resting-state functional connectivity within mesolimbic executive circuits, relationships between these measures.A case-control, magnetic resonance imaging study of healthy comparison at rest when performing Balloon Analogue Risk Task, which involves choice to pump balloon or cash out context uncertain risk. Conducted clinical research center an academic institution, involved 25 27 participants.Parametric modulation striatum right dorsolateral prefrontal cortex (rDLPFC; ie, degree changed as linear function risk potential reward), both indexed by number, connectivity, measured whole with seeds midbrain rDLPFC. Relationships outcomes were also tested.Parametric cortical striatal number taking differed group. It was stronger ventral but weaker rDLPFC than individuals. Methamphetamine-dependent exhibited greater putamen, amygdala, hippocampus (P < .05, brain, cluster corrected). This negatively related level making. In participants, parametric making positively striatum.Maladaptive methamphetamine users may reflect circuit-level dysfunction, deficits task-based activation. Heightened mesocorticolimbic system, coupled reduced create bias toward reward-driven behavior over cognitive users. Interventions improve balance enhance treatments for stimulant dependence other disorders that involve maladaptive

Language: Английский

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Obesity-Related Differences between Women and Men in Brain Structure and Goal-Directed Behavior

Frontiers in Human Neuroscience, Journal Year: 2011, Volume and Issue: 5

Published: Jan. 1, 2011

Gender differences in the regulation of body weight are well documented. Here, we assessed obesity-related influences gender on brain structure as performance Iowa Gambling Task. This task requires evaluation both immediate rewards and long-term outcomes thus mirrors trade-off between reward from eating effect overeating weight. In women, but not men, show that preference for salient face negative consequences is higher obese than lean subjects. addition, report structural left dorsal striatum (i.e. putamen) right dorsolateral prefrontal cortex women only. Functionally, regions known to play complimentary roles habitual goal-directed control behavior motivational contexts. For gray matter volume correlates positively with measures obesity coding value saliency food nucleus accumbens, orbitofrontal cortex) hypothalamus brain's central homeostatic centre). These subjects hedonic systems may reflect a bias towards energy intake exceeding actual demand. Although cannot infer our results etiology observed differences, resemble neural behavioral other forms addiction, however, marked men. findings important designing gender-appropriate treatments possibly its recognition form addiction.

Language: Английский

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Altered Frontal Cortical Volume and Decision Making in Adolescent Cannabis Users

Frontiers in Psychology, Journal Year: 2010, Volume and Issue: 1

Published: Jan. 1, 2010

Anticipating future outcomes is central to decision making and a failure consider long-term consequences may lead impulsive choices. Adolescence vulnerable period during which underdeveloped prefrontal cortical systems contribute poor judgment, choices, substance abuse. Conversely, abuse this alter neural involved in greater impulsivity. Although broad network supports undergoes extensive change adolescent development, one region that be critical the medial cortex. Altered functional integrity of specifically related reward perception, abuse, dependence. In present investigation, we acquired structural magnetic resonance images (MRI), using 3T Siemens Trio scanner, from 18 cannabis abusing adolescents (CA; 2 female 16 male subjects; mean age, 17.7 years; range 16-19 years), healthy controls (HC; 6 12 17.2 years). order measure orbital cortex (moPFC) morphology impulsivity, semi-automated reconstruction volumetric segmentation MRIs was performed with FreeSurfer. Impulsivity evaluated Barratt Impulsiveness Scale (BIS). Our results indicate have decreased right moPFC volume compared controls, p = 0.01, d 0.92, CI(0.95) 0.21, 1.59. Cannabis also show orientation, as indexed by BIS non-planning subscale, when 0.89, 0.23, 1.55. Moreover, total positively correlated age first use r (18) 0.49, < 0.03, suggesting alterations initiation or early reduced volume.

Language: Английский

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Disruption of Maternal Parenting Circuitry by Addictive Process: Rewiring of Reward and Stress Systems

Frontiers in Psychiatry, Journal Year: 2011, Volume and Issue: 2

Published: Jan. 1, 2011

Addiction represents a complex interaction between the reward and stress neural circuits, with increasing drug use reflecting shift from positive reinforcement to negative mechanisms in sustaining dependence. Preclinical studies have indicated involvement of regions within extended amygdala as subserving this transition, especially under stressful conditions. In addictive situation, system serves maintain habitual behaviors that are associated relief affect, at cost attenuating salience other rewards. Therefore, addiction reflects dysregulation core systems, including prefrontal cortex (PFC), ventral tegmental area (VTA), nucleus accumbens (NAc), well hypothalamic-pituitary-adrenal axis system. Here, we consider consequences changes function during or following on parenting, an inherently rewarding process may be disrupted by addiction. Specifically, outline preclinical human support systems contribution these parenting. Increasing evidence suggests important role for hypothalamus, PFC, VTA, NAc same being those dysregulated Moreover, addicted adults, propose parenting cues trigger reactivity rather than salience, heighten affect states, eliciting both potential parental neglect abuse.

Language: Английский

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Dopamine, Corticostriatal Connectivity, and Intertemporal Choice

Journal of Neuroscience, Journal Year: 2012, Volume and Issue: 32(27), P. 9402 - 9409

Published: July 4, 2012

Value-based decisions optimize behavioral outcomes. Because delayed rewards are discounted, an increased tendency to choose smaller, immediate can lead suboptimal choice. Steep discounting of (impulsivity) characterizes subjects with frontal lobe damage and disorders including substance abuse. Correspondingly, animal studies indirect evidence in humans suggest that lower dopamine the cortex contributes steeper by impairing corticostriatal function. To test this hypothesis directly, we performed a randomized, double-blind, counterbalanced, placebo-controlled study which administered brain penetrant catechol-O-methyltransferase inhibitor tolcapone or placebo healthy performing delay task. Tolcapone significantly choice monetary rewards, tolcapone-induced increase covaried BOLD activity left ventral putamen anterior insula. also changed connectivity: specifically, inducing decrease coherence between pregenual cingulate cortex. These results indicate raising cortical levels attenuates impulsive changing

Language: Английский

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The Central Amygdala and Alcohol: Role of -Aminobutyric Acid, Glutamate, and Neuropeptides

Cold Spring Harbor Perspectives in Medicine, Journal Year: 2012, Volume and Issue: 2(12), P. a012195 - a012195

Published: Oct. 19, 2012

Alcohol dependence is a chronically relapsing disorder characterized by compulsive drug seeking and taking, loss of control in limiting intake, the emergence withdrawal syndrome absence drug. Accumulating evidence suggests an important role for synaptic transmission central amygdala (CeA) mediating alcohol-related behaviors neuroadaptative mechanisms associated with alcohol dependence. Acute facilitates γ-aminobutyric acid-ergic (GABAergic) CeA via both pre- postsynaptic mechanisms, chronic increases baseline GABAergic transmission. inhibits glutamatergic effects at N-methyl-d-aspartate (NMDA) AMPA receptors CeA, whereas up-regulates receptor (NMDAR)-mediated Pro- (e.g., corticotropin-releasing factor [CRF]) anti-stress NPY, nociceptin) neuropeptides affect alcohol- anxiety-related behaviors, also alter alcohol-induced on neurotransmission. produces plasticity these neuropeptide systems, reflecting recruitment those systems during transition to

Language: Английский

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Putting desire on a budget: dopamine and energy expenditure, reconciling reward and resources

Frontiers in Integrative Neuroscience, Journal Year: 2012, Volume and Issue: 6

Published: Jan. 1, 2012

Accumulating evidence indicates integration of dopamine function with metabolic signals, highlighting a potential role for in energy balance, frequently construed as modulating reward response to homeostatic state. Though its precise remains controversial, the perspective has dominated investigation motivational disorders, including obesity. In hypothesis outlined here, we suggest instead that primary behavior is modulate activity adapt behavioral expenditure prevailing environmental conditions, and motivated behaviors derived from balance. Dopamine long been known activity, exemplified by psychostimulants act via dopamine. More recently, there nascent into voluntary some investigators suggesting may serve final common pathway couples sensing regulated expenditure. We interposed between input both internal external world, modulates along two axes: conserve-expend axis regulates generalized an explore-exploit axes degree which value biases distribution activity. this view, increased does not promote consumption tasty food. Instead promotes exploration while decreased favors conservation exploitation. This provides mechanistic interpretation apparent paradox: well-established food seeking findings low dopaminergic functions are associated Our alternative on obesity reinterprets 'reward deficiency hypothesis' perceived defici

Language: Английский

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