Effects of chronic chlorpromazine or lithium administration on ageing-related lipopigment in rat Purkinje neurones

Abstract

Ageing-related accumulation of neuronal lipopigment is considered to be debris from processes of renewal of cellular constituents, but can also reflect cell damage and certain diseases. Chlorpromazine (an example of a class of drug chronically administered in psychiatric practice) has been reported to reduce neuronal lipopigment accumulation, and the present study investigated the effects of 28 weeks of chlorpromazine administration on lipopigment in rat Purkinje neurones. The effects of 26 weeks of lithium administration (also chronically administered in psychiatric practice) were also studied. Lipopigment was identified by fluorescence microscopy and the area enclosed by an outline of each discrete region of lipopigment was measured. While lithium administration was not associated with significant changes in lipopigment variables, chlorpromazine administration was associated with a significant (p=0.001) reduction in the number of discrete lipopigment regions and with significant (p=0.001) differences in the numbers of discrete lipopigment regions in various size categories. The findings are similar to those associated with the administration of acetyl-L-carnitine (which has been reported to reduce some morphological and behavioural associations of brain ageing) and are compatible with a reduction in the rate of lipopigment formation. This could reflect an adverse effect of chlorpromazine administration (i.e. reduced functional activity of neurones) or a beneficial effect (i.e. a reduction in ageing-related changes).