CHRONIC HALOPERIDOL TREATMENT DIFFERENTIALLY AFFECTS THE EXPRESSION OF SYNAPTIC AND NEURONAL PLASTICITY-ASSOCIATED GENES

Synaptophysin is a protein used as a marker of presynaptic terminals, We previously showed that, in dorsolateral striatum of the rat, 2 week s' haloperidol treatment up-regulated synaptophysin mRNA, We have now investigated the effects of 16 weeks' treatment with haloperidol on sy naptophysin expression in dorsolateral striatum, frontoparietal cortex and hippocampus, in order to see if the implied haloperidol-induced s ynaptic plasticity persists. For comparison, in both the 2- and 16-wee k treatment groups we determined the mRNA abundance of the neuronal pl asticity-associated gene GAP-43, and the housekeeping gene cyclophilin , Sixteen weeks' haloperidol administration increased synaptophysin mR NA in striatum and frontoparietal cortex but not in hippocampus. The i ncrease was demonstrable both regionally and per neuron. A similar tre nd was seen for synaptophysin protein using immunoautoradiography. GAP -43 mRNA was elevated in frontoparietal cortex by 2 weeks' haloperidol but was not significantly changed in any area in the 16-week treatmen t group, Cyclophilin mRNA, a marker of overall gene expression, was un affected by haloperidol. The persistent increase in synaptophysin expr ession supports the evidence that chronic antipsychotic drug treatment induces synaptic reorganisation in some striatal and cortical neuron populations, whereas the GAP-43 mRNA data suggest that haloperidol doe s not produce a sustained alteration of neuronal plasticity, Further s tudy of plasticity-associated gene expression may be valuable in clari fying the long-term neuronal and synaptic changes produced by antipsyc hotics, and how these are related to the neurochemical effects of the drugs.