Molecular and cellular neurosciences
-
Mol. Cell. Neurosci. · Jul 2017
Effects of repeated cocaine exposure and withdrawal on voluntary ethanol drinking, and the expression of glial glutamate transporters in mesocorticolimbic system of P rats.
Glutamatergic neurotransmission within the brain's reward circuits plays a major role in the reinforcing properties of both ethanol and cocaine. Glutamate homeostasis is regulated by several glutamate transporters, including glutamate transporter type 1 (GLT-1), cystine/glutamate transporter (xCT), and glutamate aspartate transporter (GLAST). Cocaine exposure has been shown to induce a dysregulation in glutamate homeostasis and a decrease in the expression of GLT-1 and xCT in the nucleus accumbens (NAc). ⋯ Co-exposure of cocaine and ethanol decreased the relative mRNA expression and the expression of GLT-1 in the NAc but not in the medial prefrontal cortex (mPFC). Importantly, co-exposure of cocaine and ethanol decreased relative expression of xCT in the NAc but not in the mPFC. Our findings demonstrated that chronic cocaine exposure affects ethanol intake; and ethanol and cocaine co-abuse alters the expression of glial glutamate transporters.
-
Mol. Cell. Neurosci. · Jul 2017
Activation of adenosine A2A receptor signaling regulates the expression of cytokines associated with immunologic dysfunction in BTBR T+ Itpr3tf/J mice.
Autism spectrum disorder (ASD) is neurodevelopmental disorders characterized by stereotypical repetitive behavior, impaired social interaction, and deficits in communication. The BTBR T+ Itpr3tf/J (BTBR) mice have been extensively used as an animal model of the ASD-like phenotype. Adenosine A2A receptors (A2ARs) are considered potential targets in the treatment of neurodegenerative diseases. ⋯ Our results showed that the levels of IL-2+, IL-6+, IL-9+, IFN-γ+, and TNF-α+ were significantly lower, whereas the levels of TGF-β+ in the spleen and in splenic CD4+ T cells were significantly higher in the CGS-treated mice than in the BTBR control and SCH-treated mice. In addition, reverse transcription polymerase chain reaction (RT-PCR) and western blot analysis showed a decrease in the mRNA and protein expression levels of IL-2, IL-6, IL-9, IFN-γ+, and TNF-α+ and an increase in the mRNA and protein expression levels of TGF-β in the CGS-treated mice, while treatment with BTBR alone and SCH resulted in increased Th1 levels and decreased Th2 levels in the brain tissue. Our results suggest that treatment the A2AR agonist CGS may be a promising therapeutic option for neuroimmune dysfunction.