期刊
ADDICTION BIOLOGY
卷 21, 期 3, 页码 589-602出版社
WILEY
DOI: 10.1111/adb.12249
关键词
Dopamine receptors; glutamate; methamphetamine; prefrontal cortex; voltage-gated calcium channels
资金
- FONCYT-Agencia Nacional de Promocion Cientifica y Tecnologica
- BID, Argentina [1728 OC.AR.T 2012-0924, 1728 OC.AR. PICT-2012-1769]
- UBACYT [20120130101305BA]
- NIH [P20 GM103425]
- [PIP 11420100100072]
Psychostimulant addiction is associated with dysfunctions in frontal cortex. Previous data demonstrated that repeated exposure to methamphetamine (METH) can alter prefrontal cortex (PFC)-dependent functions. Here, we show that withdrawal from repetitive non-contingent METH administration (7 days, 1mg/kg) depressed voltage-dependent calcium currents (I-Ca) and increased hyperpolarization-activated cation current (I-H) amplitude and the paired-pulse ratio of evoked excitatory postsynaptic currents (EPSCs) in deep-layer pyramidal mPFC neurons. Most of these effects were blocked by systemic co-administration of the D1/D5 receptor antagonist SCH23390 (0.5 and 0.05mg/kg). In vitroMETH (i.e. bath-applied to slices from naive-treated animals) was able to emulate its systemic effects on I-Ca and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Ca(v)2.1), N-type Cacna1b (Ca(v)2.2), T-type Ca(v)3.1 Cacna1g, Ca(v)3.2 Cacna1h, Ca(v)3.3 Cacna1i and the auxiliary subunit Cacna2d1 (21); (2) hyperpolarization-activated cyclic nucleotide-gated channels Hcn1 and Hcn2; and (3) glutamate receptors subunits AMPA-type Gria1, NMDA-type Grin1 and metabotropic Grm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D1/5 receptor blockade. Altogether, these altered mechanisms affecting synaptic physiology and transcriptional regulation may underlie PFC functional alterations that could lead to PFC impairments observed in METH-addicted individuals.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据