ArticleNPJ schizophrenia2018
Medial septum activation produces opposite effects on dopamine neuron activity in the ventral tegmental area and substantia nigra in MAM vs. normal rats.
Article in NPJ schizophrenia, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 14 citations in OpenAlex.
- Sex-dependent emergence of prepubertal social dysfunction and augmented dopamine activity in a neurodevelopmental rodent model relevant for schizophrenia.Schizophrenia research · 2023Article
- Medial Prefrontal Cortex to Medial Septum Pathway Activation Improves Cognitive Flexibility in Rats.The international journal of neuropsychopharmacology · 2023Article
- Medial septum activation improves strategy switching once strategies are well-learned via bidirectional regulation of dopamine neuron population activity.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2022Article
- Nicotine Administration Normalizes Behavioral and Neurophysiological Perturbations in the MAM Rodent Model of Schizophrenia.The international journal of neuropsychopharmacology · 2021Article
- Beyond Dopamine Receptor Antagonism: New Targets for Schizophrenia Treatment and Prevention.International journal of molecular sciences · 2021Review
- The Medial Septum as a Potential Target for Treating Brain Disorders Associated With Oscillopathies.Frontiers in neural circuits · 2021Review
- Dysregulation of Midbrain Dopamine System and the Pathophysiology of Schizophrenia.Frontiers in psychiatry · 2020Review
- Hippocampal Hyperactivity as a Druggable Circuit-Level Origin of Aberrant Salience in Schizophrenia.Frontiers in pharmacology · 2020Review
- The medial septum enhances reversal learning via opposing actions on ventral tegmental area and substantia nigra dopamine neurons.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2019Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The medial septum (MS) differentially impacts midbrain dopamine (DA) neuron activity via the ventral hippocampus, a region implicated in DA-related disorders. However, whether MS regulation of ventral tegmental area (VTA) and substantia nigra pars compacta (SNc) is disrupted in a developmental disruption model of schizophrenia is unknown. Male Sprague-Dawley rats were exposed at gestational day 17 to methylazoxymethanol (MAM) or saline. As adults, NMDA (0.75 µg/0.2 µL) was infused into the MS, and either DA neuron activity in the VTA and SNc (7-9 anesthetized rats per group) or amphetamine-induced hyperlocomotion (AIH, 11-13 rats per group) was measured. MS activation produced a 58% increase in the number of spontaneously active DA neurons in VTA and a 37% decrease in SNc in saline rats. However, MS activation produced opposite effects on DA population activity in MAM rats, decreasing VTA DA activity by 51% and increasing SNc DA activity by 47%. MS activation also increased AIH by 113% in MAM rats, opposite of what is seen in intact rats. The effect in behavioral output may be due to disrupted GABAergic regulation of SNc as bicuculline infusion into vSub, which selectively prevented the MS activation-induced decrease in SNc DA activity in intact rats, prevented the increase in AIH and SNc DA activity in MAM rats. These findings demonstrate that the regulation of midbrain DA neurons by the MS is disrupted in this well-validated animal model, suggesting that it could be a potential locus for pharmacological intervention in disorders such as schizophrenia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.