Effects of acute and repeated cocaine on markers for neural plasticity within the mesolimbic system in rats.

Abstract

Repeated cocaine is known to induce morphological changes in dopaminergic circuits that are known to participate on cocaine-induced addictive changes. The objective of the present study was to discern if acute or repeated regimens of daily cocaine (10 mg/kg) lead to reliable changes in the expression of some protein markers for neural plasticity such as synaptophysin, p21-Arc, alpha-tubulin (α-tubulin), and stathmin, in the mesolimbic dopaminergic circuit. Well-known changes in tyrosine hydroxylase and protein kinase A were used for confirming biochemical effects of repeated cocaine. Animals were subjected to three treatments: acute injection, 3-day injections, or sensitizing cocaine during 3 days followed by challenging doses at days 8 and 18. The findings revealed that sensitizing regimen of cocaine increases stathmin levels within the nucleus accumbens at day 18 of treatment, not day 8, without changes of synaptophysin, p21-Arc, or α-tubulin. This neural plasticity change seems not to be related to the development of motor sensitization. Other neural regions such as prefrontal cortex, dorsal striatum, and ventral tegmental area were not found to be affected. Repeated cocaine led to well-known short-term augmentation of tyrosine-hydroxylase and protein kinase A expressions in the nucleus accumbens, as well as maintained upregulation of tyrosine hydroxylase in the ventral tegmental area. As stathmin is an important regulatory protein of microtubule dynamics, this protein change would be linked to morphological changes after repeated cocaine. It was confirmed that upregulation of tyrosine hydroxylase within the ventral tegmental area may participate on the development of motor sensitization.