scholarly journals Sex differences in methylphenidate-induced dopamine increases in ventral striatum

2021 ◽  
Author(s):  
Peter Manza ◽  
Ehsan Shokri-Kojori ◽  
Corinde E. Wiers ◽  
Danielle Kroll ◽  
Dana Feldman ◽  
...  
Keyword(s):  
Sex Differences ◽  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Drug Effects ◽  
Dopamine System ◽  
Routes Of Administration ◽  
Hyperactivity Disorder ◽  
Enhanced Sensitivity ◽  
Neuropsychiatric Diseases ◽  
The Brain

AbstractSex differences in the prevalence of dopamine-related neuropsychiatric diseases and in the sensitivity to dopamine-boosting drugs such as stimulants is well recognized. Here we assessed whether there are sex differences in the brain dopamine system in humans that could contribute to these effects. We analyzed data from two independent [11C]raclopride PET brain imaging studies that measured methylphenidate-induced dopamine increases in the striatum using different routes of administration (Cohort A = oral 60 mg; Cohort B = intravenous 0.5 mg/kg; total n = 95; 65 male, 30 female), in blinded placebo-controlled designs. Females when compared to males reported stronger feeling of “drug effects” and showed significantly greater dopamine release in the ventral striatum (where nucleus accumbens is located) to both oral and intravenous methylphenidate. In contrast, there were no significant differences in methylphenidate-induced increases in dorsal striatum for either oral or intravenous administration nor were there differences in levels of methylphenidate in plasma. The greater dopamine increases with methylphenidate in ventral but not dorsal striatum in females compared to males suggests an enhanced sensitivity specific to the dopamine reward system that might underlie sex differences in the vulnerability to substance use disorders and to attention-deficit/hyperactivity disorder (ADHD).

scholarly journals Neural population dynamics underlying expected value computation

2020 ◽  
Author(s):  
Hiroshi Yamada ◽  
Yuri Imaizumi ◽  
Masayuki Matsumoto
Keyword(s):  
Ventral Striatum ◽  
Temporal Dynamics ◽  
Dorsal Striatum ◽  
Expected Value ◽  
Economic Behavior ◽  
Neural Dynamics ◽  
Neural Population ◽  
Integrative Process ◽  
Expected Values ◽  
The Brain

AbstractComputation of expected values, i.e., probability times magnitude, seems to be a dynamic integrative process performed in the brain for efficient economic behavior. However, neural dynamics underlying this computation remain largely unknown. We examined (1) whether four core reward-related regions detect and integrate the probability and magnitude cued by numerical symbols and (2) whether these regions have distinct dynamics in the integrative process. Extractions of mechanistic structure of neural population signal demonstrated that expected-value signals simultaneously arose in central part of orbitofrontal cortex (cOFC, area 13m) and ventral striatum (VS). These expected-value signals were incredibly stable in contrast to weak and/or fluctuated signals in dorsal striatum and medial OFC. Notably, temporal dynamics of these stable expected-value signals were unambiguously distinct: sharp and gradual signal evolutions in cOFC and VS, respectively. These intimate dynamics suggest that cOFC and VS compute the expected-values with unique time constants, as distinct, partially overlapping processes.

scholarly journals Roles for the Dorsal Striatum in Aversive Behavior

2021 ◽  
Vol 15 ◽  
Author(s):  
Adrien T. Stanley ◽  
Pellegrino Lippiello ◽  
David Sulzer ◽  
Maria Concetta Miniaci
Keyword(s):  
Ventral Striatum ◽  
Dorsal Striatum ◽  
Inhibitory Avoidance ◽  
Cell Types ◽  
Aversive Learning ◽  
Stimulus Response ◽  
Aversive Behavior ◽  
Established Role ◽  
The Brain

The ability to identify and avoid environmental stimuli that signal danger is essential to survival. Our understanding of how the brain encodes aversive behaviors has been primarily focused on roles for the amygdala, hippocampus (HIPP), prefrontal cortex, ventral midbrain, and ventral striatum. Relatively little attention has been paid to contributions from the dorsal striatum (DS) to aversive learning, despite its well-established role in stimulus-response learning. Here, we review studies exploring the role of DS in aversive learning, including different roles for the dorsomedial and dorsolateral striatum in Pavlovian fear conditioning as well as innate and inhibitory avoidance (IA) behaviors. We outline how future investigation might determine specific contributions from DS subregions, cell types, and connections that contribute to aversive behavior.

scholarly journals A Neurodevelopmental Model of Combined Pyrethroid and Chronic Stress Exposure

Toxics ◽  
2019 ◽  
Vol 7 (2) ◽  
pp. 24
Author(s):  
Aimée I. Vester ◽  
Merry Chen ◽  
Carmen J. Marsit ◽  
W. Michael Caudle
Keyword(s):  
Chronic Stress ◽  
Dorsal Striatum ◽  
Environmental Exposures ◽  
Dopamine System ◽  
Fast Scan Cyclic Voltammetry ◽  
Hyperactivity Disorder ◽  
Neurodevelopmental Model ◽  
Y Maze ◽  
Dopaminergic Dysfunction ◽  
Increased Activity

Attention-deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders of childhood and previous studies indicate the dopamine system plays a major role in ADHD pathogenesis. Two environmental exposures independently associated with dopaminergic dysfunction and ADHD risk include exposure to deltamethrin, a pyrethroid insecticide, and chronic stress. We hypothesized that combined neurodevelopmental exposure to both deltamethrin and corticosterone (CORT), the major stress hormone in rodents, would result in additive changes within the dopamine system. To study this, we developed a novel dual exposure paradigm and exposed pregnant C57BL/6 dams to 3 mg/kg deltamethrin through gestation and weaning, and their offspring to 25 μg/mL CORT dissolved in the drinking water through adulthood. Midbrain RNA expression as well as striatal and cortical protein expression of key dopaminergic components were investigated, in addition to ADHD-like behavioral tasks and electrochemical dopamine dynamics via fast-scan cyclic voltammetry. Given the well-described sexual dimorphism of ADHD, males and females were assessed separately. Males exposed to deltamethrin had significantly decreased midbrain Pitx3 expression, decreased cortical tyrosine hydroxylase (TH) expression, increased activity in the Y maze, and increased dopamine uptake rate in the dorsal striatum. These effects did not occur in males exposed to CORT only, or in males exposed to both deltamethrin and CORT, suggesting that CORT may attenuate these effects. Additionally, deltamethrin- and CORT-exposed females did not display these dopaminergic features, which indicates these changes are sex-specific. Our results show dopaminergic changes from the RNA through the functional level. Moreover, these data illustrate the importance of testing multiple environmental exposures together to better understand how combined exposures that occur in certain vulnerable populations could affect similar neurodevelopmental systems, as well as the importance of studying sex differences of these alterations.

scholarly journals The mouse cortico-basal ganglia-thalamic network

2020 ◽  
Author(s):  
Nicholas N. Foster ◽  
Laura Korobkova ◽  
Luis Garcia ◽  
Lei Gao ◽  
Marlene Becerra ◽  
...  
Keyword(s):  
Basal Ganglia ◽  
Functional Organization ◽  
Network Motif ◽  
Dorsal Striatum ◽  
Thalamic Nuclei ◽  
Cortical Areas ◽  
Neuropsychiatric Diseases ◽  
History Of ◽  
Input Source ◽  
The Brain

ABSTRACTThe cortico-basal ganglia-thalamic loop is one of the fundamental network motifs in the brain. Revealing its structural and functional organization is critical to understanding cognition, sensorimotor behavior, and the natural history of many neurological and neuropsychiatric diseases. Classically, the basal ganglia is conceptualized to contain three primary information output channels: motor, limbic, and associative. However, given the roughly 65 cortical areas and two dozen thalamic nuclei that feed into the dorsal striatum, a three-channel view is overly simplistic for explaining the myriad functions of the basal ganglia. Recent works from our lab and others have subdivided the dorsal striatum into numerous functional domains based on convergent and divergent inputs from the cortex and thalamus. To complete this work, we generated a comprehensive data pool of ∼700 injections placed across the striatum, external globus pallidus (GPe), substantia nigra pars reticulata (SNr), thalamic nuclei, and cortex. We identify 14 domains of SNr, 36 in the GPe, and 6 in the parafascicular and ventromedial thalamic nuclei. Subsequently, we identify 6 parallel cortico-basal ganglia-thalamic subnetworks that sequentially transduce specific subsets of cortical information with complex patterns of convergence and divergence through every elemental node of the entire cortico-basal ganglia loop. These experiments reveal multiple important novel features of the cortico-basal ganglia network motif. The prototypical sub-network structure is characterized by a highly interconnected nature, with cortical information processing through one or more striatal nodes, which send a convergent output to the SNr and a more parallelized output to the GPe; the GPe output then converges with the SNr. A domain of the thalamus receives the nigral output, and is interconnected with both the striatal domains and the cortical areas that filter into its nigral input source. This study provides conceptual advancement of our understanding of the structural and functional organization of the classic cortico-basal ganglia network.

Sex Differences in Cognition

2019 ◽  
pp. 41-66
Author(s):  
Elizabeth Hampson
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Sex Differences ◽  
Spatial Cognition ◽  
Sex Steroids ◽  
Cognitive Functions ◽  
Laboratory Animals ◽  
Human Central Nervous System ◽  
The Brain

Organizational and activational effects of sex steroids were first discovered in laboratory animals, but these concepts extend to hormonal actions in the human central nervous system. This chapter begins with a brief overview of how sex steroids act in the brain and how the organizational-activational hypothesis originated in the field of endocrinology. It then reviews common methods used to study these effects in humans. Interestingly, certain cognitive functions appear to be subject to modification by sex steroids, and these endocrine influences may help explain the sex differences often seen in these functions. The chapter considers spatial cognition as a representative example because the spatial family of functions has received the most study by researchers interested in the biological roots of sex differences in cognition. The chapter reviews evidence that supports an influence of both androgens and estrogens on spatial functions, and concludes with a glimpse of where the field is headed.

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