Dopamine D1 receptor activation of adenylyl cyclase, not phospholipase C, in the nucleus accumbens promotes maternal behavior onset in rats

Abstract A body of evidence supports the idea that the mesolimbic dopamine (DA) system modulates the natural increase in responsiveness female rats show toward offspring (biological or foster) at birth. In the absence of the full hormonal changes associated with pregnancy and birth, female rats do not show immediate responsiveness toward foster offspring. Activation of the mesolimbic DA system can produce an immediate onset of maternal behavior in these females. For example, female rats that are hysterectomized and ovariectomized on day 15 of pregnancy (15HO) and presented with pups 48 hours later normally show maternal behavior after 2–3 days of pup exposure, but will show maternal behavior on day 0 of testing after microinjection of the DA D 1 receptor agonist, SKF 38393, into the nucleus accumbens (NA) at the time of pup presentation. DA D 1 receptor stimulation is known to activate cAMP intracellular signaling cascades via its stimulation of adenylyl cyclase (AC). However, some DA D 1 receptors are also linked to phospholipase C (PLC) and are capable of activating phosphatidylinositol signaling cascades. SKF 38393 stimulates both types of D 1 receptors. Here we provide evidence that the facilitatory effects of DA D 1 receptor stimulation in the NA on maternal behavior are mediated by AC-linked DA D 1 receptors. By examining the effects of intra-NA application of SKF 83822, a drug which selectively binds DA D 1 –AC receptors, or SKF 83959, a drug which selectively activates D 1 –PLC-linked receptors, we find that only SKF 83822 facilitates maternal behavior onset.