In vitro progesterone modulation of amphetamine-stimulated dopamine release from the corpus striatum of ovariectomized estrogen-treated female rats: response characteristics

Abstract

We have previously reported that a pulsatile infusion of progesterone directly into superfusion chambers containing corpus striatal tissue fragments of ovariectomized estrogen-treated female rats augmented amphetamine-stimulated dopamine release in vitro. In an attempt to understand some of the means by which progesterone modulates dopamine release under these in vitro conditions, we examined two characteristics of this effect of progesterone. First, to determine the threshold dose of progesterone and whether it was necessary for progesterone to be administered in a pulsatile mode, in Expt. I we examined the effect of a single, brief infusion of progesterone at doses of 2, 4 and 40 ng/ml. Second, to evaluate the temporal relationship between progesterone infusion and its capacity to augment amphetamine-stimulated dopamine release, in Expt. II we varied the interval between progesterone infusion and amphetamine challenge, with amphetamine infused at 10, 30, 50 or 90 min post-progesterone. The results of Expt. I indicate that a single 10-min infusion of progesterone at 2 ng/ml was adequate to produce an accentuated response to amphetamine infusion. Although further increases were obtained following the 4 and 40 ng/ml doses, these values failed to differ significantly from the levels obtained with the 2 ng/ml dose. From Expt. II, we observed that this effect of progesterone was relatively rapid with statistically significant increase in amphetamine-stimulated dopamine release occurring at 30 min post-progesterone and similar responses being maintained at 50 and 90 min post-progesterone. These results demonstrate that a single brief exposure to progesterone results in a rapid increase in the capacity of striatal dopaminergic terminals to respond to amphetamine and suggests the activation of a non-genomic process leading to an increase in dopamine available for release from dopamine nerve terminals.