The effect of prolonged administration of lithium on the level of dopamine D2 receptor mRNA in the rat striatum and nucleus accumbens

Abstract

To explore associations of neostriatal (NST) endogenous levels of dopamine (DA) and serotonin (5-HT) with sensitivity of their receptors, graded doses of 6-hydroxydopamine HBr (0 to 400 micrograms, ICV; 6-OHDA; desipramine pretreatment, 20 mg/kg IP) were given to rats between birth (P0) and P42. Numbers of vacuous chewing movements (VCMs) induced by SKF 38393 or m-chlorophenylpiperazine (m-CPP), respective DA D1 and 5-HT2 agonists, were subsequently determined. Enhanced SKF 38393-induced VCMs occurred when NST DA was reduced 97%–98% by high dose 6-OHDA (100–134 micrograms) at P0 or P3, but not in rats with 95%–97% loss in DA produced by 6-OHDA at P7 (134 micrograms) or P3 (67 micrograms), Enhanced m-CPP-induced VCMs occurred even when NST 5-HT content was not elevated after 6-0HDA (134 micrograms at P10). Accordingly, D1 and 5-HT receptor sensitivity is not correlated with respective NST DA and 5-HT contents. The stage of ontogeny at the time of DA denervation may be the governing influence on receptor sensitivity.