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Biomedical subjects

Clinton B McCracken

Publications and source records attributed to Clinton B McCracken.

4 recordsLinked to original sources

A single evoked afterdischarge produces rapid time-dependent changes in connexin36 protein expression in adult rat dorsal hippocampus.

Gap junctions between neurons contribute to synchronous neuronal firing and may play a role in the pathophysiology of epilepsy. We examined the expression of a number of gap junction subunits, including the neuronal gap junction forming protein connexin36 (Cx36), in the hippocampus at various time points following an electrically stimulated afterdischarge (AD) in freely-moving animals. Once recovered from electrode implantation, animals were tested with an escalating series of stimulations until an AD was evoked. Suprathreshold stimulation produced a brief AD with no convulsion. Groups of animals were sacrificed at 3, 12, and 24h post-stimulation, and connexin expression was assessed via semiquantitative immunoblotting. Compared to implanted non-stimulated controls, a significant decrease in Cx36 expression was observed in the stimulated dorsal hippocampus at 3h post-stimulation, which returned to control levels by 24h. No changes were seen in the ventral hippocampus. As well, no changes were seen in other selected connexin proteins including Cx26, Cx32, and Cx43, thought to be expressed primarily in glia, in either dorsal or ventral hippocampus. These data suggest that a relatively brief hypersynchronous neuronal discharge can produce rapid and specific changes in Cx36 expression, which may have implications for both normal brain function and the pathophysiology of epilepsy.

Action Potentials↗

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.

Animals↗

Amphetamine withdrawal produces region-specific and time-dependent changes in connexin36 expression in rat brain.

Repeated amphetamine treatment produces a long-lasting augmentation of locomotor behavior in rats, a phenomenon known as behavioral sensitization. This process is thought to be a correlate of the addictive process in humans, and it is believed that there are drug-induced neuroadaptations that underlie these behavioral changes. One mechanism by which amphetamine can alter brain function is by affecting direct intercellular communication between neurons via gap junctions. The purpose of the present study was to examine the effect of an amphetamine treatment regimen known to produce changes in dye coupling between neurons, a functional correlate of gap junction function, on the expression of the neuronal gap junction-forming protein, connexin36. Here we report that withdrawal from an extended amphetamine regimen produces region-specific and time-dependent changes in connexin36 expression in rat nucleus accumbens and prefrontal cortex, brain regions known play roles in sensitization and addiction. This is, to our knowledge, the first demonstration of pharmacological manipulation of connexin36 in vivo.

Amphetamine↗