Alterations in BDNF and trkB mRNAs following acute or sensitizing cocaine treatments and withdrawal.

In the present study, we used in situ hybridization to examine the influence of acute or repeated cocaine administrations and withdrawal from repeated cocaine treatment on the level of brain-derived neurotrophic factor (BDNF) and its receptor trkB mRNAs in rat brain. Cocaine (10 mg/kg i.p.) injected acutely produced locomotor hyperactivation, while repeated (single injection for 5 days) administrations of cocaine (10 mg/kg) induced a two-fold increases in the locomotor activity in rats in response to a challenge cocaine dose (10 mg/kg) on day 10, as compared to the saline-treated animals (sensitization). Cocaine treatments induced a brain-region-specific decrease in the levels of trkB mRNA. On the other hand, BDNF mRNA in the rat hippocampus was increased only in the group of rats subjected to cocaine withdrawal. Animals under cocaine withdrawal demonstrated a significant increase in the immobility time measured by the use of modified forced swimming test. Therefore, the increases in the levels of BDNF mRNA in the rat hippocampus seem to be correlated with "depressive-like" behavioral effects during withdrawal from repeated cocaine treatment. In the shell (but not in the core) of the nucleus accumbens, the levels of BDNF mRNA were significantly increased following acute and repeated cocaine treatment as well as during cocaine withdrawal, which indicates that the alterations in the neurotrophin level in the brain region important for the expression of cocaine-induced sensitization involve other mechanisms.