Disruptions in serotonergic regulation of cortical glutamate release in primate insular cortex in response to chronic ethanol and nursery rearing

Abstract Early-life stress has been shown to increase susceptibility to anxiety and substance abuse. Disrupted activity within the anterior insular cortex (AIC) has been shown to play a role in both of these disorders. Altered serotonergic processing is implicated in controlling the activity levels...

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Bibliographic Details
Published in:Neuroscience 2012-04, Vol.207, p.167-181
Main Authors: Alexander, G.M, Graef, J.D, Hammarback, J.A, Nordskog, B.K, Burnett, E.J, Daunais, J.B, Bennett, A.J, Friedman, D.P, Suomi, S.J, Godwin, D.W
Format: Article
Language:English
Subjects:
5-HT1A
Alcohol-Induced Disorders, Nervous System - metabolism
Alcohol-Induced Disorders, Nervous System - physiopathology
Alcoholism - metabolism
Alcoholism - physiopathology
Alcoholism and acute alcohol poisoning
Animals
anterior insula
Biological and medical sciences
Central Nervous System Depressants - toxicity
Cerebral Cortex - physiopathology
Cerebral Cortex - secretion
Chronic Disease
Disease Models, Animal
ethanol
Ethanol - toxicity
Female
Fundamental and applied biological sciences. Psychology
Glutamic Acid - secretion
Macaca mulatta
Male
Maternal Deprivation
Medical sciences
Neurology
Receptors, Serotonin - physiology
serotonin
stress
Stress, Psychological - etiology
Stress, Psychological - metabolism
Stress, Psychological - physiopathology
Toxicology
Vertebrates: nervous system and sense organs
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Summary:Abstract Early-life stress has been shown to increase susceptibility to anxiety and substance abuse. Disrupted activity within the anterior insular cortex (AIC) has been shown to play a role in both of these disorders. Altered serotonergic processing is implicated in controlling the activity levels of the associated cognitive networks. We therefore investigated changes in both serotonin receptor expression and glutamatergic synaptic activity in the AIC of alcohol-drinking rhesus monkeys. We studied tissues from male rhesus monkeys raised under two conditions: Male rhesus monkeys (1) “mother reared” (MR) by adult females ( n =9) or (2) “Nursery reared” (NR), that is, separated from their mothers and reared as a separate group under surrogate/peer-reared conditions ( n =9). The NR condition represents a long-standing and well-validated nonhuman primate model of early life stress. All monkeys were trained to self-administer ethanol (4% w/v) or an isocaloric maltose–dextrin control solution. Subsets from each rearing condition were then given daily access to ethanol, water, or maltose–dextrin for 12 months. Tissues were collected at necropsy and were further analyzed. Using real time RT-PCR we found that ethanol-naive, NR monkeys had lower AIC levels of 5-HT1A and 5-HT2A receptor mRNA compared with ethanol-naive, MR animals. Although NR monkeys consumed more ethanol over the 12-month period compared with MR animals, both MR and NR animals expressed greater 5-HT1A and 5-HT2A receptor mRNA levels following chronic alcohol self-administration. The interaction between nursery-rearing conditions and alcohol consumption resulted in a significant enhancement of both 5-HT1A and 5-HT2A receptor mRNA levels such that lower expression levels observed in nursery-rearing conditions were not found in the alcohol self-administration group. Using voltage clamp recordings in the whole cell configuration we recorded excitatory postsynaptic currents in both ethanol-naive and chronic self-administration groups of NR and MR monkeys. Both groups that self-administered ethanol showed greater glutamatergic activity within the AIC. This AIC hyperactivity in MR alcohol-consuming monkeys was accompanied by an increased sensitivity to regulation by presynaptic 5-HT1A receptors that was not apparent in the ethanol-naive, MR group. Our data indicate that chronic alcohol consumption leads to greater AIC activity and may indicate a compensatory upregulation of presynaptic 5-HT1A receptors. O
ISSN:0306-4522
1873-7544
DOI:10.1016/j.neuroscience.2012.01.027