PMID- 10510198 OWN - NLM STAT- MEDLINE DCOM- 19991124 LR - 20231213 IS - 0953-816X (Print) IS - 0953-816X (Linking) VI - 11 IP - 9 DP - 1999 Sep TI - Long-term changes in connexin32 gap junction protein and mRNA expression following cocaine self-administration in rats. PG - 3329-38 AB - Considerable evidence indicates a critical role for dopamine in the reinforcing effects of cocaine. Because dopamine has been shown to be a critical modulator of gap junction communication in both eye and brain, we sought to examine whether extended intravenous cocaine self-administration would affect the expression of gap junction channel-forming proteins (connexins). Using ELISA, Western analysis, immunohistochemistry, semi-quantitative reverse transcriptase polymerase chain reaction (RT-PCR), and non-radioactive in situ hybridization, we demonstrate that withdrawal from chronic cocaine self-administration causes lasting changes in connexin32 (Cx32) expression in the nucleus accumbens and hippocampus at 2, 7 and 21 days after the last cocaine injection. A sustained decrease in Cx32 protein and mRNA levels is noted in areas that have been implicated in cocaine craving (i.e. nucleus accumbens and subfields of the hippocampal formation). A progressive increase in gap junction protein and mRNA expression is noted in areas that become hyperexcitable 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 abuse. FAU - Bennett, S A AU - Bennett SA AD - Institute of Biochemistry, Carleton University, Ottawa, ON, Canada. FAU - Arnold, J M AU - Arnold JM FAU - Chen, J AU - Chen J FAU - Stenger, J AU - Stenger J FAU - Paul, D L AU - Paul DL FAU - Roberts, D C AU - Roberts DC LA - eng GR - GM37551/GM/NIGMS NIH HHS/United States PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - France TA - Eur J Neurosci JT - The European journal of neuroscience JID - 8918110 RN - 0 (Connexins) RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (RNA, Messenger) RN - I5Y540LHVR (Cocaine) SB - IM MH - Animals MH - Antibody Specificity MH - Blotting, Western MH - Cocaine/adverse effects/*pharmacology MH - Connexins/*biosynthesis/immunology MH - Dopamine Uptake Inhibitors/adverse effects/*pharmacology MH - Enzyme-Linked Immunosorbent Assay MH - Epilepsy/chemically induced MH - Gap Junctions/drug effects/*metabolism MH - Hippocampus/metabolism MH - Immunohistochemistry MH - In Situ Hybridization MH - Injections MH - Male MH - Neostriatum/metabolism MH - Nucleus Accumbens/metabolism MH - RNA, Messenger/*biosynthesis/genetics MH - Rats MH - Rats, Wistar MH - Reverse Transcriptase Polymerase Chain Reaction MH - Self Administration MH - Substance Withdrawal Syndrome/metabolism MH - Gap Junction beta-1 Protein EDAT- 1999/10/06 00:00 MHDA- 1999/10/06 00:01 CRDT- 1999/10/06 00:00 PHST- 1999/10/06 00:00 [pubmed] PHST- 1999/10/06 00:01 [medline] PHST- 1999/10/06 00:00 [entrez] AID - ejn752 [pii] AID - 10.1046/j.1460-9568.1999.00752.x [doi] PST - ppublish SO - Eur J Neurosci. 1999 Sep;11(9):3329-38. doi: 10.1046/j.1460-9568.1999.00752.x.