Estrogens Modulate the Responsiveness of <i>in vivo</i> Recorded Striatal Neurons to lontophoretic Application of Dopamine in Rats: Role of D₁ and D₂2 Receptor Activation

Abstract

Abstract Estrogens are known to affect the functioning of the extrapyramidal motor system. Their actions concern both pre- and postsynaptic components of the dopaminergic nigrostriatal neurotransmission. Postsynaptically, estradiol alters the electrophysiological responses of striatal neurons to dopamine application. The aim of this study was to determine the respective roles of D(1) and D(2) receptor subtypes in this modification of dopamine action. Eighty-three spontaneously firing caudate neurons of ovariectomized female rats were extracellularly recorded during iontophoretic ejection of dopamine or dopaminergic agonists or antagonists. Between 5 and 10 h after a single 17beta-estradiol injection (60 mug/kg), the predominant effect of dopamine was an activation of firing (63%), and the distribution of responses significantly differed from controls and from neurons recorded less than 5 h after estradiol injection (P<0.001) on which dopamine mainly elicited inhibitory effects (71% and 63%, respectively). The excitatory effects of dopamine on this subset of spontaneously firing striatal neurons were blocked by the D(1) antagonist SCH 23390 (56%), whereas the inhibitory actions were antagonized by sulpiride (62%), whose isolated application often had an excitatory effect (54%). The distributions of the responses to specific D(1) or D(2) agonists were not altered by estrogen treatment: the predominant effect of the D(2) agonist RU 24213 was in all groups a reduction of firing rate (54%), and the D(1) agonist SKF 38393 mainly induced either a decrease in mean firing rate (21%) or a biphasic effect consisting on an excitation-inhibition sequence (53%). These results suggest that estradiol does not qualitatively alter the coupling of D(1) or D(2) receptors to their electrophysiological effectors, but rather quantitatively changes the ratio between the D(1) and D(2) receptor-mediated components of dopamine actions, reinforcing the D(1) and/or attenuating the D(2) receptor-mediated component.