Maternal Protein Deficiency Causes Region‐Specific and Sex‐Dependent Changes in 5‐HT1A Receptor Function in Adult Offspring

Abstract

Protein insufficiency, rather than caloric restriction, during pregnancy leads to abnormalities in emotion and cognition in adult offspring. However, the underlying neural mechanisms are unclear. In rats, we examined serotonin1A (5‐HT1A) receptor function in adult offspring of mothers that were free‐fed standard (20%) or low (10%) protein isocaloric chow during pregnancy. Importantly, the maternal low protein diet did not affect the body weight of mothers or offspring. At P110‐117, 5‐HT1A receptor agonist DPAT (0.01‐1mg/kg, ip) induced stereotypic behaviors were measured. The potency of DPAT to induce flat body posture and lower lip retraction was reduced in female offspring, as indicated by rightward shifts (~3 fold) in the dose‐response curves. In littermates, we used quantitative autoradiography to measure the capacity of 5‐HT1A receptors to activate G proteins. The maternal low protein diet resulted in a 50% decrease in DPAT (1μM)‐stimulated [35S]GTPΥS binding in hippocampus of female offspring, with no change in frontal cortex, suggesting a region‐specific down‐regulation of postsynaptic 5‐HT1A receptor function. DPAT (1μM)‐stimulated [35S]GTPΥS binding was increased (54%) in dorsal raphe of female offspring, suggesting enhanced inhibition of serotonin neuronal activity. By contrast, no significant change in 5‐HT1A receptor function was observed in male offspring. Both in vivo and ex vivo data indicate that maternal protein deficiency causes profound region‐specific and sex‐dependent changes in 5‐HT1A receptor function, which may underlie abnormal emotion and cognition in adult offspring. Supported by Morrison Trust