Assessment of tyrosine hydroxylase immunoreactive innervation in five subregions of the nucleus accumbens shell in rats treated with repeated cocaine

To explore the effects of behavioral sensitization on the anatomy of the nucleus accumbens shell, we employed a typical cocaine dosing paradigm and assessed tyrosine hydroxylase immunoreactive varicosities in five different areas of the shell, as well as the core of the nucleus accumbens. Rats were given bidaily injections of either saline (1 ml/kg i.p.) or cocaine (15 mg/kg i.p.) for 5 consecutive days, and sacrificed either 2 or 14 days from the last injection. Sections of the nucleus accumbens were processed for tyrosine hydroxylase immunoreactivity and the number of immunoreactive varicosities in contact with neuronal cell bodies was quantified in each of the subregions of the shell, as well as the core of the nucleus accumbens. Compared to saline controls, the cocaine‐treated animals showed a significant augmentation in tyrosine hydroxylase immunoreactivity in two of the five subregions after 2 days of withdrawal in the shell, but not in the core. No differences were found in any region tested after 14 days of withdrawal. These data are the first to suggest that increases in nucleus accumbens presynaptic tyrosine hydroxylase may play a role in the development of behavioral sensitization, but not in the long‐term expression of this phenomenon. Synapse 38:261–270, 2000. © 2000 Wiley‐Liss, Inc.