Increased pentobarbital insensitivity in hypoglossal (XII) motoneurons during late pregnancy is consistent with increased epsilon subunit expression in GABAA receptors (GABAARs)

Abstract

Progesterone and allopregnanolone (ALLO) are increased centrally during late pregnancy. Increased ALLO creates a risk for excessive neuronal inhibition because ALLO is a positive allosteric modulator of GABAARs. We hypothesized that XII motoneurons compensate for increased inhibition during late pregnancy by increasing epsilon subunit expression in GABAARs because the epsilon subunit confers insensitivity to positive allosteric modulators, such as ALLO and pentobarbital. To test this question, medullary slices were taken from G18 pregnant rats (n=7), adult male (n=5), and adult female (n=2) rats. Extracellular multichannel electrodes recorded spontaneous action potentials in XII motoneurons. To pharmacologically test for epsilon subunits, slices were sequentially exposed to 200 and 300 μM pentobarbital (45 min each). During the last 15 min of 300 μM pentobarbital, XII motoneuron firing rates steadily decreased to 37±9% (n=105 cells) and 36±5% (n=32 cells) of baseline in slices from male and female rats, respectively. In contrast, XII motoneuron firing rates from G18 rat slices increased to 120±29% of baseline (n=78 cells). These data show that pregnancy caused XII motoneurons to become more resistant to positive allosteric modulation by pentobarbital. We speculate that increased epsilon expression prevents excessive ALLO‐dependent inhibition during pregnancy. Supported by NIH T32 HL07654.