Expression of complexin I and II mRNAs and their regulation by antipsychotic drugs in the rat forebrain

Complexin (cx) I and II are homologous synaptic protein genes which are dif ferentially expressed in mouse and human brain and differentially affected in schizophrenia. We characterized the distribution of ex I and II mRNAs in rat forebrain and examined whether their abundance, or the transcript of t he synaptic marker synaptophysin, is affected by 14 days' administration of antipsychotic drugs (haloperidol, chlorpromazine, risperidone, olanzapine, or clozapine). Cx I mRNA predominated in medial habenula, medial septum-di agonal band complex, and thalamus, whereas ex II mRNA was more abundant in most other regions, including isocortex and hippocampus. Within the hippoca mpus, ex I mRNA was primarily expressed by interneurons and ex II mRNA by g ranule cells and pyramidal neurons. Localized ex II mRNA signal was seen in the dentate gyrus molecular layer, suggestive of its transport into granul e cell. dendrites. Antipsychotic treatment produced selective, modest effec ts on ex mRNA expression. Cx I mRNA was elevated by olanzapine in dorsolate ral striatum and frontoparietal cortex, while the abundance of ex II mRNA r elative to ex I mRNA was decreased in both areas by olanzapine and haloperi dol. Chlorpromazine increased ex II mRNA in frontoparietal cortex and synap tophysin mRNA in dorsolateral striatum. In summary, the data have implicati ons both for understanding the effects of antipsychotic medication on synap tic organization, and for synaptic protein expression studies in patients t reated with the drugs. (C) 2000 Wiley-Liss, Inc.