Persistent alterations in dendrites, spines, and dynorphinergic synapses in the nucleus accumbens shell of rats with neuroleptic-induced dyskinesias

Chronic treatment of humans or experimental animals with classical neurolep tic drugs can lead to abnormal, tardive movements that persist long after t he drugs are withdrawn. A role in these neuroleptic-induced dyskinesias may be played by a structural change in the shell of the nucleus accumbens whe re the opioid peptide dynorphin is upregulated in treated rats that show va cuous chewing movements (VCMs). The shell of the nucleus accumbens normally contains a dense plexus of dynorphinergic fibers especially in its caudome dial part. After 27 weeks of haloperidol administration and 18 weeks of wit hdrawal, the immunoreactive labeling of this plexus is intensified when com pared with that after vehicle treatment. In addition, medium spiny neurons here show a significant increase in spine density, dendritic branching, and numbers of terminal segments. In the VCM-positive animals, the dendritic s urface area is reduced, and dynorphin-positive terminals contact more spine s and form more asymmetrical specializations than do those in animals witho ut the syndrome (VCM-negative and vehicle-treated groups). Persistent, neur oleptic-induced oral dyskinesias could therefore be caused by incontroverti ble alterations, involving terminal remodeling or sprouting, to the synapti c connectivity of the accumbal shell.