Chronic cocaine administration depletes tyrosine hydroxylase immunoreactivity in the meso-limbic dopamine system in...

Chronic administration of cocaine (10 mg/kg, IP, every 12 hours for 10 consecutive days) produced a large decrease in tyrosine hydroxylase staining axons and terminal boutons in the frontal cortex and nucleus accumbens in rats. This treatment also produced a depletion of tyrosine hydroxylase immunoreactivity in the ventral tegmental area of the midbrain when examined 60 days following the final cocaine injection. These effects were quantitated using a Leitz Data Acquisition and Display System. This analysis revealed a 59% and 65% decrease in tyrosine hydroxylase positive staining terminal processes in the frontal cortex and nucleus accumbens, respectively. Furthermore, quantitative light microscopic analysis showed a 52% decrease in tyrosine hydroxylase positive material in the ventral tegmental area. These data demonstrate that chronic administration of cocaine produces a long-term, if not permanent, loss of tyrosine hydroxylase enzyme in both the cell bodies of the midbrain ventral tegmental area as well as in the nerve terminals in post-synaptic target regions of the forebrain.