Dopamine release and uptake are greater in female than male rat striatum as measured by fast cyclic voltammetry

The present studies investigated sexual dimorphisms in dopamine release and uptake using fast-scan cyclic voltammetry in anesthetized rats and in brai n slices. Electrical stimulation of the medial forebrain bundle of anesthet ized rats at high frequency (60 Hz) elicited significantly more extracellul ar dopamine in the caudate nucleus of females than males. This sex differen ce was apparent over a range of current intensities applied to the stimulat ing electrode. Local electrical stimulation of brain slices in vitro verifi ed in vivo results as more extracellular dopamine was elicited by single an d 10 pulse stimulations in the caudate nucleus of females. Kinetic analysis of in vivo and in vitro dopamine overflow data indicated that dopamine rel ease (the concentration of dopamine released per stimulus pulse) and the ma ximal velocity of dopamine uptake are greater in female rats, but the affin ity of the transporter for dopamine was the same in males and females. None of these three parameters varied across the female estrous cycle. Linear r egression analysis of dopamine release versus maximal uptake velocity data indicated a significant association of release and uptake sites in each sex and regression lines for males and females virtually overlapped. One explanation for these results is greater dopamine neuron terminal densi ty in female caudate nucleus. These sexual dimorphisms in dopaminergic neur otransmission provide a novel, plausible mechanism to explain robust sex di fferences in behavioral responses of rats to pyschostimulant drugs and may have implications for human neurological disorders and drug abuse. (C) 1999 IBRO. Published by Elsevier Science Ltd.