Dopamine and 5-HT receptor sensitivity does not correlate with neostriatal dopamine or 5-HT content

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 (P 0) and P 42. 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 P 0 or P 3, 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-OHDA (134 micrograms at P 10). 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.