We continued to study several aspects of the action of psychotropic drugs. In cultured rat cerebellar granule cells, carbamazepine (CBZ) was found to induce neurotoxicity, which can be demonstrated by biochemical measurement and morphological examination. Our recent results show that CBZ-induced neurotoxicity is associated with fragmentation of DNA, suggesting that apoptosis has occurred. Several lines of evidence support the notion that CBZ interacts with NMDA receptors, perhaps as an antagonist. CBZ-induced neurotoxicity and DNA fragmentation can be blocked by NMDA. NMDA also prevents glutamate-induced death of cerebellar granule cells. Another psychotropic drug, lithium, at therapeutically relevant concentrations (< 2 mM) is neurotrophic for cerebellar granule cells and increases the level of m3-muscarinic receptor mRNA but decreases m2-receptor mRNA level. At higher concentrations, lithium induces neurotoxicity which is not prevented by the presence of NMDA or myo-inositol. The effects of CBZ and lithium on hippocampal cell cultures are being examined. In a collaborative effort, chronic haloperidol treatment of rats was found to decrease dopamine-stimulated phosphoinositide (PI) turnover, but there was an increase of dopamine D2 receptor number in the striatum. Moreover, the haloperidol's effect on dopamine- sensitive PI turnover may be secondarily related to an increase in dopamine D2 receptor density.
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