Chronic oral olanzapine treatment but not haloperidol decreases [3H] MK-801 binding in the rat brain Independent of dietary conditions. (11th June 2022)

• Record Type: Journal Article
• Authors: Waldman, Leah; Richardson, Brittany; Hamilton, John; Thanos, Panayotis
• Is Part Of: Neuroscience letters. Volume 781(2022)
• Publication Date: 2022-06-11
• Subjects: Neuroleptics -- Haloperidol -- Olanzapine -- High-fat diet -- Autoradiography -- Schizophrenia -- Antipsychotics -- NMDA -- Glutamate; Neurology -- Periodicals; Neurology -- Periodicals; Research -- Periodicals; Neurologie -- Périodiques; Neuroanatomie -- Périodiques; Neuropharmacologie -- Périodiques; Neurophysiologie -- Périodiques; Neurology; Periodicals; Electronic journals; 617.48
• DOI: 10.1016/j.neulet.2022.136657
• Languages: English
• ISSNs: 0304-3940

Abstract

Highlights: Haloperidol and Olanzapine are among the most commonly prescribed neuroleptics to treat schizophrenia. Schizophrenia pathophysiology may be characterized by glutamatergic NMDA-related dysfunctions. There is evidence that high fat dietary conditions impact glutamate neurotransmission and NMDA receptor functioning. NMDA receptor binding was assessed via [ 3 H] MK-801 autoradiography after chronic neuroleptics and a high fat diet. Independent of diet, chronic oral olanzapine decreased [ 3 H] MK-801 binding across multiple regions of the brain. Abstract: Haloperidol and olanzapine are first and second-generation antipsychotic (neuroleptic) medications approved to treat schizophrenia. Glutamate signaling is known to play an important role in the manifestation of schizophrenia symptoms, as phencyclidine, a non-competitive N-methyl-D-aspartate receptor (NMDAR) antagonist, replicates and exasperates these symptoms. While initial reports show that neuroleptic treatments can impact aspects of NMDAR expression, there is little attention on the interaction between neuroleptics and dietary conditions. Thus, we examined the impact of chronic haloperidol and olanzapine treatment under both normal and high-fat dietary conditions on NMDAR expression. Adult male rats were treated for 28-days with either oral vehicle, haloperidol (1.5 mg/kg), or olanzapine (10 mg/kg), and fed either a standard control diet or a high-fat diet. In-vitro receptor autoradiography binding was performed using [ 3 H] MK-801 as a measure of NMDAR expression. Results showed that olanzapine, irrespective of the diet, significantly decreased [ 3 H] MK-801 binding within the cingulate cortex, substantia nigra, insular cortex, piriform cortex, ectorhinal cortex and perirhinal cortex, the forelimb region of the somatosensory cortex, and all quadrants of the caudate-putamen. In contrast, haloperidol treatment did not impact [ 3 H] MK-801 binding, and we also report no effect of diet on [ 3 H] MK-801 binding. These data suggest that the effects seen in olanzapine treatment are not mediated by diet, nor does a 28-day chronic high-fat diet alter [ 3 H] MK-801 binding. Furthermore, these data also importantly support that combined consumption of a high-fat diet and pharmacological treatments are not immediately detrimental to NMDARs and contribute to the expansive literature of precision medicine.