Pretreatment with antisense oligodeoxynucleotide against D(2) or D(3) receptor mRNA diminished dopamine's inhibitory effect on dorsomedial arcuate neurons in brain slices of estrogen-treated ovariectomized rats

A high percentage of dopamine (DA)-responsive neurons has been repeatedly shown in hypothalamic dorsomedial arcuate nucleus (dmARN) using single-unit recording in brain slices. Both D(2) and D(3) receptors may be involved in the inhibitory action of DA as indicated by results obtained from using specific DA agonists and antagonists. To further delineate the DA receptor types involved, ovariectomized, estrogen-primed Sprague-Dawley rats pretreated with antisense oligodeoxynucleotide (ODN, 10 microg/3 microl, i.c.v.) against either D(2) or D(3) receptor mRNA for 2 days were used in this study for brain slice preparation. Rats pretreated with aCSF, random antisense or sense ODNs were used as controls. DA (5-50 nmol) inhibited a majority of dmARN neurons in brain slices prepared from rats pretreated with aCSF (71.4% of 35 U), random antisense/sense ODN for D(2) (67.6%, n=34), D(3) (59.5%, n=42), or D(2) plus D(3) (60.5%, n=38) mRNAs. In contrast, DA inhibited 43.6% (n=39) of dmARN neurons in slices prepared from D(2), and 38.5% (n=39) from D(3) antisense ODN-pretreated rats. Furthermore, in brain slices prepared from rats pretreated with combined D(2) and D(3) antisense ODNs, DA only inhibited 18.4% (n=38) of dmARN neurons. We conclude that both D(2) and D(3) receptors are involved in the action of DA on dmARN neurons in ovariectomized, estrogen-treated rats.