The effect of striatal dopamine depletion on striatal and cortical glutamate: A mini-review

Abstract

Understanding the interplay between the neurotransmitters dopamine and glutamate in the striatum has become the highlight of several theories of neuropsychiatric illnesses, such as schizophrenia. Using in vivo brain imaging in humans, alterations in dopamine and glutamate concentrations have been observed in several neuropsychiatric disorders. However, it is unclear a priori how alterations in striatal dopamine should modulate glutamate concentrations in the basal ganglia. In this selective mini-review, we examine the consequence of reducing striatal dopamine functioning on glutamate concentrations in the striatum and cortex; regions of interest heavily examined in the human brain imaging studies. We examine the predictions of the classical model of the basal ganglia, and contrast it with findings in humans and animals. The review concludes that chronic dopamine depletion (>4 months) produces decreases in striatal glutamate levels which are consistent with the classical model of the basal ganglia. However, acute alterations in striatal dopamine functioning, specifically at the D2 receptors, may produce opposite affects. This has important implications for models of the basal ganglia and theorizing about neurochemical alterations in neuropsychiatric diseases. Moreover, these findings may help guide a priori hypotheses for 1H-MRS studies measuring glutamate changes given alterations in dopaminergic functioning in humans.

Anti‐GAPDH Autoantibodies as a Pathogenic Determinant and Potential Biomarker of Neuropsychiatric Diseases

“…In the ORT performance measure, a preference for the novel object is considered to be an index of consolidated memory for the familiar object (35). Overall, object investigation did not differ between anti-GAPDH-treated mice and untreated control mice (F [1,12] 5 2.609, P 5 0.1322). However, the discrimination index (measuring memory retention) was worse in anti-GAPDH-treated mice compared with untreated controls (F [1,11] In the EPM apparatus, only anti-GAPDHtreated mice showed a reduced latency to immobility (F [1,11] 5 5,150, P 5 0.0444) ( Figure 4B) in addition to an increased frequency of, and trend toward, a higher duration of this behavior in the open arms of the maze, suggesting that emotionality was increased in the anti-GAPDH-treated mice (F [2,24] 5 3.636, P 5 0.0417 for frequency; F [2,24] 5 2.872, P 5 0.0762 for duration).…”

“…However, the discrimination index (measuring memory retention) was worse in anti-GAPDH-treated mice compared with untreated controls (F [1,11] In the EPM apparatus, only anti-GAPDHtreated mice showed a reduced latency to immobility (F [1,11] 5 5,150, P 5 0.0444) ( Figure 4B) in addition to an increased frequency of, and trend toward, a higher duration of this behavior in the open arms of the maze, suggesting that emotionality was increased in the anti-GAPDH-treated mice (F [2,24] 5 3.636, P 5 0.0417 for frequency; F [2,24] 5 2.872, P 5 0.0762 for duration). Anti-GAPDH-treated mice also tended to show a reduced latency to the stretched-attend posture (F [1,12] 5 3.850, P 5 0.0733), a behavior that is indicative of an anxiety-like profile.…”

“…The origin and pathophysiology of these multifactorial and complex disorders are largely unknown and poorly understood. In addition to a role of genetic, neuropathologic, and environmental factors , growing evidence supports a crucial role of autoimmunity in the development of neuropsychiatric disorders . A connection between autoimmunity and neuropsychiatric disturbance is supported by the following findings: 1) the often‐observed comorbidity of autoimmune diseases, such as systemic lupus erythematosus (SLE), and neuropsychiatric disorders; and 2) significant increases in the levels of circulating autoantibodies against various molecules expressed in different brain regions in patients with neuropsychiatric disorders .…”

The relationship between subcortical brain volume and striatal dopamine D2/3 receptor availability in healthy humans assessed with [11C]‐raclopride and [11C]‐(+)‐PHNO PET

“…In turn, striatal glutamate levels were found to be negatively correlated with dorsal caudate volumes in these patients [Plitman et al, ]. Given the potential interactions between striatal DA and glutamate [Caravaggio et al, ; Stone et al, ], it can be inferred that the dopaminergic changes observed in schizophrenia may also be related changes in brain morphology. However, without direct evidence this remains merely conjuncture.…”

Neuronutrient Amino-Acid Therapy Protects Against Reward Deficiency Syndrome: Dopaminergic Key to Homeostasis and Neuroplasticity

“…That idea that NAc dopamine maintains and controls our normal drives relating to pleasure is well established [172][173][174]. In fact, dopamine is thought of as the anti-stress and pleasure molecule [175][176][177][178][179]. Synaptic release of dopamine stimulates some receptors (D1-D5), leading to increased feelings of well-being and stress reduction [180][181][182].…”