GABAergic and glutamatergic effects on nigrostriatal and mesolimbic dopamine release in the rat

Nikolaus, Susanne; Beu, Markus; Wittsack, Hans‐Jörg; Müller‐Lutz, Anja; Antke, Christina; Hautzel, Hubertus; Mori, Yuriko; Mamlins, Eduards; Antoch, Gerald; Müller, Hans‐Wilhelm

doi:10.1515/revneuro-2019-0112

Cited by 2 publications

(2 citation statements)

References 100 publications

(139 reference statements)

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“…Nikolaus and colleagues presented a series of experiments exploring the effects of agonists and antagonists at both GABA A receptors and NMDARs on dopamine controls in mesolimbic and mesostriatal pathways. They observed that the GABA A receptor agonist muscimol and the NMDAR antagonist amantadine exert similar actions on regional dopamine release, supporting the hypothesis of triple glutamate—GABA—dopamine interaction underlying the dysfunctions observed in schizophrenia [ 89 , 90 ].…”

Section: Dopamine–glutamate Interaction and The Role Of D-amino Acidsmentioning

confidence: 85%

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

et al. 2022

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Schizophrenia has been conceptualized as a neurodevelopmental disorder with synaptic alterations and aberrant cortical–subcortical connections. Antipsychotics are the mainstay of schizophrenia treatment and nearly all share the common feature of dopamine D2 receptor occupancy, whereas glutamatergic abnormalities are not targeted by the presently available therapies. D-amino acids, acting as N-methyl-D-aspartate receptor (NMDAR) modulators, have emerged in the last few years as a potential augmentation strategy in those cases of schizophrenia that do not respond well to antipsychotics, a condition defined as treatment-resistant schizophrenia (TRS), affecting almost 30–40% of patients, and characterized by serious cognitive deficits and functional impairment. In the present systematic review, we address with a direct and reverse translational perspective the efficacy of D-amino acids, including D-serine, D-aspartate, and D-alanine, in poor responders. The impact of these molecules on the synaptic architecture is also considered in the light of dendritic spine changes reported in schizophrenia and antipsychotics’ effect on postsynaptic density proteins. Moreover, we describe compounds targeting D-amino acid oxidase and D-aspartate oxidase enzymes. Finally, other drugs acting at NMDAR and proxy of D-amino acids function, such as D-cycloserine, sarcosine, and glycine, are considered in the light of the clinical burden of TRS, together with other emerging molecules.

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Section: Dopamine–glutamate Interaction and The Role Of D-amino Acidsmentioning

confidence: 85%

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

et al. 2022

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“…We summarize this D2-dependent inhibitory effect on V 0 to be a rate constant k V times the current D2 AR value. In addition to the D2-dependent inhibitory regulation through negative feedback, midbrain DAergic neurons also exhibit D2-independent excitatory coupling through positive PLOS COMPUTATIONAL BIOLOGY feedback [98][99][100]. These excitatory effects are defined as proportional to the current firing rate F times a rate constant b that reflects the conversion strength from neuron activity to neuron electrochemical state.…”

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confidence: 99%

A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

Zhang,

Ralph,

Stinchcombe

2024

PLoS Comput Biol

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Many self-motivated and goal-directed behaviours display highly flexible, approximately 4 hour ultradian (shorter than a day) oscillations. Despite lacking direct correspondence to physical cycles in the environment, these ultradian rhythms may be involved in optimizing functional interactions with the environment and reflect intrinsic neural dynamics. Current evidence supports a role of mesostriatal dopamine (DA) in the expression and propagation of ultradian rhythmicity, however, the biochemical processes underpinning these oscillations remain to be identified. Here, we use a mathematical model to investigate D2 autoreceptor-dependent DA self-regulation as the source of ultradian behavioural rhythms. DA concentration at the midbrain-striatal synapses is governed through a dual-negative feedback-loop structure, which naturally gives rise to rhythmicity. This model shows the propensity of striatal DA to produce an ultradian oscillation characterized by a flexible period that is highly sensitive to parameter variations. Circadian (approximately 24 hour) regulation consolidates the ultradian oscillations and alters their response to the phase-dependent, rapid-resetting effect of a transient excitatory stimulus. Within a circadian framework, the ultradian rhythm orchestrates behavioural activity and enhances responsiveness to an external stimulus. This suggests a role for the circadian-ultradian timekeeping hierarchy in governing organized behaviour and shaping daily experience through coordinating the motivation to engage in recurring, albeit not highly predictable events, such as social interactions.

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GABAergic and glutamatergic effects on nigrostriatal and mesolimbic dopamine release in the rat

Cited by 2 publications

References 100 publications

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

Rational and Translational Implications of D-Amino Acids for Treatment-Resistant Schizophrenia: From Neurobiology to the Clinics

A mathematical model for the role of dopamine-D2 self-regulation in the production of ultradian rhythms

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