Isolation rearing-induced reduction of brain 5α-reductase expression: Relevance to dopaminergic impairments

被引：39

作者：

Bortolato, Marco ^{[1
,2
,3
]}

Devoto, Paola ^{[2
,4
]}

Roncada, Paola ^{[5
]}

Frau, Roberto ^{[2
,3
]}

Flore, Giovanna ^{[3
]}

Saba, Pierluigi ^{[4
]}

Pistritto, Giuseppa ^{[6
]}

Soggiu, Alessio ^{[4
]}

Pisanu, Salvatore ^{[7
]}

Zappala, Agata ^{[8
]}

Ristaldi, Maria Serafina ^{[9
]}

Tattoli, Maria ^{[10
]}

Cuomo, Vincenzo ^{[11
]}

Marrosu, Francesco ^{[2
,3
]}

Barbaccia, Maria Luisa ^{[6
]}

机构：

[1] Univ So Calif, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Univ Cagliari, Centro Interdipartimentale Sindrome Tourette, Cagliari, Italy

[3] Univ Cagliari, Dept Cardiovasc & Neurol Sci, Cagliari, Italy

[4] Univ Cagliari, Dept Neurosci Bernard B Brodie, Cagliari, Italy

[5] Ist Sperimentale Italiano Lazzaro Spallanzani, Milan, Italy

[6] Univ Roma Tor Vergata, Dept Neurosci, Pharmacol Sect, Sch Med, I-00133 Rome, Italy

[7] Proteotech Srl, Pula, CA, Italy

[8] Univ Catania, Dept Physiol Sci, Catania, Italy

[9] CNR, Inst Neurogenet & Neuropharmacol, Selargius, CA, Italy

[10] Univ Bari, Dept Pharmacol & Human Physiol, Bari, Italy

[11] Univ Rome Sapienza, Dept Physiol & Pharmacol Vittorio Erspamer, Rome, Italy

来源：

NEUROPHARMACOLOGY | 2011年 / 60卷 / 7-8期

关键词：

5; alpha-reductase; Isolation rearing; Dopamine; Nucleus accumbens; Medial prefrontal cortex; GABA(A) RECEPTOR FUNCTION; TERM SOCIAL-ISOLATION; ISOLATION-REARED RATS; 5; ALPHA-REDUCTASE; PREFRONTAL CORTEX; PREPULSE INHIBITION; PROTEIN EXPRESSION; DOWN-REGULATION; MESSENGER-RNA; ALLOPREGNANOLONE;

D O I：

10.1016/j.neuropharm.2011.01.013

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Isolation rearing (IR), a well-established rat model of early chronic psychosocial stress, engenders marked behavioral alterations related to changes of dopamine (DA) neurotransmission in cortical and subcortical brain regions. Stress-induced shifts in gamma-aminobutyric acid (GABA)-ergic signaling have been implicated in the dysregulation of DA release. The neurosteroid 3 alpha-hydroxy-5 alpha-pregnan-20-one (allo-pregnanolone/AP), synthesized from progesterone by the action of the rate-limiting enzyme 5 alpha-reductase (5AR), is a potent positive allosteric modulator of GABA(A) receptor function. Thus, alterations of 5AR activity/expression may impact upon DA neurotransmission. We studied the effects of IR on the 5AR expression/function and extracellular concentrations of DA and its metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) in the rat nucleus accumbens (NAcc) and medial prefrontal cortex (mPFC). Immediately after weaning, male rats were subjected to either IR or social rearing (SR) conditions for 5-8 weeks. Compared to SR, IR rats exhibited significantly lower protein expression of 5AR isoforms (1 and 2) in both brain regions and reduced brain, but not plasma, content of AP and allotetrahydrodeoxycorticosterone, the 5 alpha-reduced metabolite of deoxycorticosterone. IR-exposed rats also exhibited higher levels of DA and DOPAC in the NAcc shell, but not in mPFC, when compared to SR rats. The 5AR inhibitor finasteride (FIN, 100 mg/kg, i.p.) enhanced DA and DOPAC content in the NAcc shell of SR, but not IR rats. FIN, however, elicited equivalent increases in DA and DOPAC levels in the mPFC of both groups. These results show that IR induces changes in expression/activity of brain 5AR which, in a brain-region specific manner, may partially underlie the alterations in DA signaling induced by this manipulation. This article is part of a Special Issue entitled 'Trends in Neuropharmacology: In Memory of Erminio Costa'. (C) 2011 Elsevier Ltd. All rights reserved.

引用

页码：1301 / 1308

页数：8

共 63 条

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