Activation of Central D-1 Dopamine Receptors Stimulates Oxytocin Release in the Lactating Rat: Evidence for Involvement of the Hypothalamic Paraventricular and Supraoptic Nuclei

Abstract

The stimulatory effect of dopamine (DA) on the release of oxytocin (OT) in lactating rats is exerted at the D-1 DA receptor subtype. Because the neural loci mediating this effect have not been identified, the objective of the present studies was to test whether OT release in the lactating rat would be elevated after central administration of a D-1 DA receptor agonist into the third ventricle (3V) or directly into either the rostral paraventricular/anterior commissural nucleus area (PVN/ACN), the central paraventricular nucleus area, or the supraoptic nucleus (SON), all of which contain OT neurosecretory cells. Lactating rats were implanted with a stainless steel cannula directed into one of the above areas or into the arcuate-ventromedial region of the medial basal hypothalamus (MBH), or sites dorsal to the PVN/ACN or SON, which served as anatomical controls. After 6-7 days of recovery, each animal received an intra-atrial cannula for sequential blood sampling, and was used in experiments 24 h later. Animals were separated from their litters, and following a period of basal blood sampling, received central microinjections of either vehicle, the D-1 DA receptor agonist SKF-38393, or the D-2 DA receptor agonist quinpirole, and blood samples were removed periodically for 60 min. An injection of angiotensin II (Ang II, 100 ng) was made into each site as a positive control for OT release. Injection of SKF-38393 (12.5 or 50 µg/5 µl) into the 3V resulted in a statistically significant and dose-releated increase in plasma OT concentrations, which was attenuated by intravenous pretreatment with the specific D-1 DA receptor antagonist, SCH-23390 (1.2 mg/kg). Unilateral injection of SKF-38393 (8 µg) into the SON region also produced a significant increase in plasma OT concentrations, while more modest increases followed injection of this agent into the PVN sites. Systemic pretreatment with the D-1 DA antagonist also blocked the effect of SKF-38393 in the SON. Plasma OT concentrations were not significantly changed after administration of SKF-38393 into the MBH or to dorsal control sites, or after any central injections of vehicle or the D-2 agonist quinpirole. Ang II markedly stimulated OT release after administration to 3V, PVN, SON and MBH, but not to the control sites dorsal to the PVN and SON. The present findings extend previous observations that D-1 DA receptors mediate the central dopaminergic stimulation of OT secretion in the lactating rat, and suggest that the SON region may be an important locus for this effect.

Central Stimulation of Oxytocin Release in the Lactating Rat by N-Methyl-D-Aspartate: Requirement for Coactivation through Non-NMDA Glutamate Receptors or the Glycine Coagonist Site

“…Fifteen minutes later, all animals received an injection of angiotensin II (All. 100 pmol in 1 pi), and blood was withdrawn at 1.5 and 10 min, to verify correct cannula placement [39]. Protocol 1 was also used in the case of NMDA/D-scrine treatment at the SSON control site, and in con trol collections involving intravenous injection of NMDA and D-serine.…”

The effects of dopaminergic/serotonergic reuptake inhibition on maternal behavior, maternal aggression, and oxytocin in the rat

“…Dopamine system stimulation through the use of agonists, particularly D2 receptor agonists, has been shown to promote the release of peripheral oxytocin (Amico et al, 1992(Amico et al, , 1993Crowley et al, 1992;Parker and Crowley, 1992), while administration of dopamine antagonists results in a significant disruption in pup retrieval, nest building, and motor activity in general (Byrnes et al, 2002;Giordano et al, 1990;Keer and Stern, 1999;Silva et al, 2001Silva et al, , 2003Stern and Keer, 1999). As Stern and Keer (1999) suggest, this could potentially be due to the dopamine system involvement in motivation and reward.…”

Impact of gestational cocaine treatment or prenatal cocaine exposure on early postpartum oxytocin mRNA levels and receptor binding in the rat

“…Manipulations of the dopamine system have been strongly associated with alterations in various aspects of maternal behavior and affect aspects of oxytocin. D2 receptor agonists particularly promote the release of peripheral oxytocin (Amico et al, 1992;Amico et al, 1993;Crowley et al, 1992;Parker and Crowley, 1992), while administration of dopamine antagonists results in a significant disruption in pup retrieval, nest building, and motor activity in general (Byrnes et al, 2002;Giordano et al, 1990;Keer and Stern, 1999;Silva et al, 2001;Silva et al, 2003;Stern and Keer, 1999).…”