Long-term changes in connexin32 gap junction protein and mRNA expression following cocaine self-administration in rats

Considerable evidence indicates a critical role for dopamine in the reinfor cing effects of cocaine. Because dopamine has been shown to be a critical m odulator of gap junction communication in both eye and brain, we sought to examine whether extended intravenous cocaine self-administration would affe ct the expression of gap junction channel-forming proteins (connexins). Usi ng ELISA, Western analysis, immunohistochemistry, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and non-radioactive in s itu hybridization, we demonstrate that withdrawal from chronic cocaine self -administration causes lasting changes in connexin32 (Cx32) expression in t he nucleus accumbens and hippocampus at 2, 7 and 21 days after the last coc aine injection. A sustained decrease in Cx32 protein and mRNA levels is not ed in areas that have been implicated in cocaine craving (i.e. nucleus accu mbens and subfields of the hippocampal formation). A progressive increase i n gap junction protein and mRNA expression is noted in areas that become hy perexcitable after chronic cocaine exposure (i.e. CA1 hippocampal neurons). We speculate that gap junction communication may be critically involved in reinforcement processes and neuroadaptive changes produced by drugs of abu se.