Maternal separation interferes with developmental changes in brain vasopressin and oxytocin receptor binding in male rats

Brain vasopressin V1A receptors (V1A-R) and oxytocin receptors (OT-R) are important modulators of social behaviors. We recently showed that exposure to maternal separation (MS; 3 h daily, postnatal days 1–14) induces changes in social behaviors in juvenile and adult male rats. Here, we hypothesize that MS induces brain region-specific changes in V1A-R and OT-R across development, which in turn, may underlie MS-induced changes in social behaviors. We examined the effects of MS on V1A-R and OT-R binding in forebrain regions of juvenile (5 weeks), adolescent (8 weeks), and adult (16 weeks) male rats. Robust age-related changes were found for V1A-R and OT-R binding in several brain regions. For example, in the lateral septum V1A-R binding increased while OT-R binding decreased with age. Most notably, OT-R binding in the caudate putamen showed a 2-fold decrease while OT-R binding in the ventromedial hypothalamus showed a 4-fold increase with age. Importantly, exposure to MS interfered with these developmental changes in several brain regions. Specifically, MS significantly increased V1A-R binding in the piriform cortex (at adolescent and adult ages), the lateral septum (at juvenile age), the hypothalamic attack area (at adolescent age), and the dentate gyrus of the hippocampus (at adolescent age), and decreased V1A-R binding in the arcuate nucleus (at juvenile age). Moreover, OT-R binding was significantly lower in the agranular cortex (at juvenile and adolescent age), the lateral septum (at adult age) and the caudate putamen (at adult age), but higher in the medial preoptic area (at adolescent age) and ventromedial hypothalamus (at adult age) after exposure to MS. In conclusion, age-dependent changes in V1A-R and OT-R binding are likely associated with the maturation of behaviors, such as sexual and aggressive behaviors, while disruption of these changes by MS might contribute to previously observed changes in social behaviors after MS.