Effect of chronic olanzapine treatment on striatal synaptic organization

Our previous work has shown that chronic haloperidol treatment decreases st riatal symmetric synapses preferentially in rats which develop oral dyskine sias (vacuous chewing movements (VCMs)). The present experiment tests the h ypothesis that olanzapine, which does not cause dyskinesia in humans or rat s, would not cause the ultrastructural changes produced by haloperidol. Aft er 6 months of treatment, VCM scores for the olanzapine group (5.1 +/- 4.5) were similar to those of controls (5.2 +/- 3.9), whereas rats in the halop eridol group were either nondyskinetic (4.3 +/- 2.2) or dyskinetic (16.9 +/ - 6.7). The volume of the striatum (mm(3)), did not differ among the groups : control, 37.5 +/- 4.7; olanzapine, 36.4 +/- 4.3; haloperidol, nondyskinet ic, 40.5 +/- 6.3; haloperidol, dyskinetic, 36.6 +/- 5.9. Synaptic density ( per 1 mum(3)), obtained from the central region of the striatum, did not di ffer between the olanzapine (0.699 +/- 0.146) and control groups (0.652 +/- 0.108). The number of asymmetric synapses in the olanzapine group (0.624 /- 0.136) was also similar to that of controls (0.550 +/- 0.090). The numbe r of symmetric synapses in the olanzapine group (0.074 +/- 0.032) was not s ignificantly different from that of controls (0.096 +/- 0.043). Thus, olanz apine, in contrast to haloperidol, did not produce dyskinesias or synapse l oss. These results strengthen the correlation between the expression of VCM s and striatal synaptic changes and indicate that olanzapine has fewer beha vioral and anatomical side effects than does haloperidol. (C) 2001 Wiley-Li ss, Inc.