Abstract:
:Atypical antipsychotic drugs (AAPDs) are widely used in children and adolescents to treat a variety of psychiatric disorders. However, little is known about the long-term effects of AAPD treatment before the brain is fully developed. Indeed, we and others have previously reported that treatment of adolescent rats with olanzapine (OLA; a widely prescribed AAPD) on postnatal days 28-49, under dosing conditions that approximate those employed therapeutically in humans, causes long-term behavioral and neurobiological perturbations. We have begun to study the mechanisms of these effects. Dopamine (DA) and serotonin (5HT) regulate many neurodevelopmental processes. Currently approved AAPDs exert their therapeutic effects principally through their DAergic activities, although in schizophrenia (SZ) and some other diseases for which AAPDs are prescribed, DAergic dysfunction is accompanied by abnormalities of glutamatergic (GLUergic) and γ-aminobutyric acidergic (GABAergic) transmission. Here, we use proton magnetic resonance spectroscopy ((1)H MRS) to investigate the effects of adolescent OLA administration on GABA and GLU levels. We found that the treatment caused long-term reductions in the levels of both GLU and GABA in the nucleus accumbens (NAc) of adult rats treated with OLA during adolescence. The NAc is a key node in the brain's "reward" system, whose function is also disrupted in schizophrenia. Further research into potential, OLA-induced changes in the levels of GLU and GABA in the NAc and other brain areas, and the dynamics and mechanisms of those changes, are an essential step for devising new adjunct therapies for existing AAPDs and for designing new drugs that increase therapeutic effects and reduce long-term abnormalities when administered to pediatric patients.
journal_name
Schizophr Resjournal_title
Schizophrenia researchauthors
Xu S,Gullapalli RP,Frost DOdoi
10.1016/j.schres.2014.10.034subject
Has Abstractpub_date
2015-02-01 00:00:00pages
452-7issue
2-3eissn
0920-9964issn
1573-2509pii
S0920-9964(14)00603-3journal_volume
161pub_type
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pub_type: 杂志文章,随机对照试验
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pub_type: 杂志文章,meta分析,评审
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doi:10.1016/j.schres.2009.05.031
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pub_type: 杂志文章
doi:10.1016/j.schres.2016.04.036
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pub_type: 杂志文章,多中心研究
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pub_type: 临床试验,杂志文章,随机对照试验
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pub_type: 杂志文章,meta分析
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