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Methamphetamine blunts Ca 2+ currents and excitatory synaptic transmission through D 1/5 receptor‐mediated mechanisms in the mouse medial prefrontal cortex
Author(s) -
González Betina,
RiveroEcheto Celeste,
Muñiz Javier A.,
Cadet Jean Lud,
GarcíaRill Edgar,
Urbano Francisco J.,
Bisagno Verónica
Publication year - 2016
Publication title -
addiction biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.445
H-Index - 78
eISSN - 1369-1600
pISSN - 1355-6215
DOI - 10.1111/adb.12249
Subject(s) - excitatory postsynaptic potential , meth , neuroscience , neurotransmission , postsynaptic current , nmda receptor , ampa receptor , prefrontal cortex , glutamate receptor , chemistry , bursting , methamphetamine , hcn channel , metabotropic glutamate receptor , postsynaptic potential , voltage dependent calcium channel , medicine , endocrinology , receptor , biology , ion channel , calcium , inhibitory postsynaptic potential , cognition , monomer , organic chemistry , acrylate , polymer
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, 1 mg/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/D 5 receptor antagonist SCH 23390 (0.5 and 0.05 mg/kg). In vitro METH (i.e. bath‐applied to slices from naïve‐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 C acna1a ( C a v 2.1), N ‐type C acna1b ( C a v 2.2), T ‐type C a v 3.1 C acna1g , C a v 3.2 C acna1h , C a v 3.3 C acna1i and the auxiliary subunit C acna2d1 (α2δ1); (2) hyperpolarization‐activated cyclic nucleotide‐gated channels H cn1 and H cn2 ; and (3) glutamate receptors subunits AMPA ‐type G ria1 , NMDA ‐type G rin1 and metabotropic G rm1 in the mouse mPFC after repeated METH treatment. Moreover, we show that some of these changes in mRNA expression were sensitive D 1/5 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.