ACTIVATION OF CORTICOSTRIATAL PATHWAY LEADS TO SIMILAR MORPHOLOGICAL-CHANGES OBSERVED FOLLOWING HALOPERIDOL TREATMENT

Treatment with haloperidol, a dopamine receptor D-2 antagonist, for on e month resulted in an increase in the mean percentage of asymmetric s ynapses containing a discontinuous, or perforated, postsynaptic densit y (PSD) [Meshul et al. (1994) Brain Res., 648:181-195] and a change in the density of striatal glutamate immunoreactivity within those presy naptic terminals [Meshul and Tan (1994) Synapse, 18:205-217]. We specu lated that this haloperidol-induced change in glutamate density might be due to an activation of the corticostriatal pathway. To determine i f activation of this pathway leads to similar morphological changes pr eviously described following haloperidol treatment, GABA (10(-5) M, 0. 5 mu l) was injected into the thalamic motor (VL/VM) nuclei daily for 3 weeks. This treatment resulted in an increase in the mean percentage of striatal asymmetric synapses containing a perforated PSD and an in crease in the density of glutamate immunoreactivity within nerve termi nals of asymmetric synapses containing a perforated or non-perforated PSD. Subchronic injections of GABA into the thalamic somatosensory nuc lei (VPM/VPL) had no effect on the mean percentage of synapses with pe rforated PSDs but resulted in a small, but significant, increase in de nsity of glutamate immunoreactivity. Using in vivo microdialysis, an a cute injection of GABA (10(-5) M, 15 mu l) into VL/VM resulted in a pr olonged rise in the extracellular level of striatal glutamate. The inc rease in asymmetric synapses with perforated PSDs and in glutamate imm unoreactivity within nerve terminals of the striatum following either subchronic haloperidol treatment or GABA injections into VL/VM suggest that an increase in glutamate release may be a common factor in these two experiments. It is possible that the extrapyramidal side effects associated with haloperidol treatment may be due, in part, to an incre ase in release of glutamate within the corticostriatal pathway. (C) 19 96 Wiley-Liss, Inc.