info:eu-repo/semantics/article
Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex
Date
2016-05Registration in:
Gonzalez, Betina; Rivero Echeto, Maria Celeste Solange; Muñiz, Javier Andrés; Cadet, Jean Lud; Garcia Rill, Edgar; et al.; Methamphetamine blunts Ca2+ currents and excitatory synaptic transmission through D1/5 receptor-mediated mechanisms in the mouse medial prefrontal cortex; Wiley Blackwell Publishing, Inc; Addiction Biology; 21; 3; 5-2016; 589-602
1355-6215
CONICET Digital
CONICET
Author
Gonzalez, Betina
Rivero Echeto, Maria Celeste Solange
Muñiz, Javier Andrés
Cadet, Jean Lud
Garcia Rill, Edgar
Urbano Suarez, Francisco Jose
Bisagno, Veronica
Abstract
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 (ICa) and increased hyperpolarization-activated cation current (IH) 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 0.05 mg/kg). In vitroMETH (i.e. bath-applied to slices from naïve-treated animals) was able to emulate its systemic effects on ICa and evoked EPSCs paired-pulse ratio. We also provide evidence of altered mRNA expression of (1) voltage-gated calcium channels P/Q-type Cacna1a (Cav2.1), N-type Cacna1b (Cav2.2), T-type Cav3.1 Cacna1g, Cav3.2 Cacna1h, Cav3.3 Cacna1i and the auxiliary subunit Cacna2d1 (α2δ1); (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.