Involvement of Protein Kinase A in Oxytocin Neuronal Activity in Rat Dams with Pup Deprivation

Oxytocin (OT) neuronal activity is the key factor for breastfeeding and it can be disrupted by mother-baby separation. To explore cellular mechanisms underlying OT neuronal activity, we studied the role of protein kinase A (PKA) in OT neuronal activity in the supraoptic nucleus (SON) using a rodent model of pup deprivation (PD) Intermittent (IPD) or continuous (CPD) PD significantly reduced suckling duration and number of milk ejections in lactating rats, particularly those with CPD. In Western blots of the SON, PD increased expressions of OT receptor (OTR) and its immediate downstream effectors, G alpha q and G beta subunits, particularly IPD, but reduced the expression of catalytic subunit of PKA (cPKA). In brain slices, inhibition of PKA blocked prostaglandin E-2-evoked increase in firing activity including burst firing in OT neurons. In IPD dams, filamentous actin formed ring-like structures in the cytoplasmic region of OT neurons, which was reduced in CPD. Moreover, molecular association between actin and cPKA also reduced in PD dams. Incubation of brain slices with OT reduced the expression of cPKA, which was blocked by pretreatment with atosiban, an antagonist of OTR. These results indicate that PD disrupts OT neuronal activity through dissociating the Gq proteins and PKA in OTR-associated signaling cascade, which couples with reduced interactions between filamentous actin and PKA in OT neurons in the SON. This study highlights that PKA can be a novel target treating abnormal OT neuronal activity and its associated diseases.

Automated summary

Continuous mother-baby separation disrupts oxytocin neuronal activity by affecting the OTR-associated signaling cascade and reducing interactions between filamentous actin and PKA in OT neurons. These findings suggest that PKA could be a potential target for treating abnormal oxytocin neuronal activity and associated diseases.