Extended cocaine self-administration and deprivation produces region-specific and time-dependent changes in connexin36 expression in rat brain

Cocaine addiction is a disease that develops over time, and it is thought that drug-induced neuro-adaptations underlie the changes in behavior seen across the addictive process. While a number of alterations in synaptic transmission have been identified, little is currently known regarding cocaine's effects on gap junctional communication between neurons. Here we examine the effects of a cocaine self-administration regimen, previously shown to increase the reinforcing efficacy of cocaine, on the expression of the neuron-specific gap junction-forming protein connexin36 (C x 36). Using real-time RT-PCR and immunoblotting, we show that binge cocaine self-administration produces region-specific and time-dependent changes in C x 36 mRNA and protein expression in the nucleus accumbens, prefrontal cortex, and hippocampus. A number of changes in C x 36 were present 1 day and 7 days following self-administration, and C x 36 mRNA and protein appeared to be differentially regulated in a region-specific manner. C x 36 protein was significantly decreased in the prefrontal cortex 7 days following self-administration, a time point when behavioral sensitization to the reinforcing effects of cocaine is observed. These results suggest that changes in neuronal gap junction expression may be one mechanism by which cocaine self-administration produces enduring changes in behavior.