Effects of Pregnancy and Progesterone on the Consumption of Ethanol by the High Ethanol Preferring (Hep) Rat

Abstract

A significant fraction of women continue to drink heavily during pregnancy, which is associated with the fetal alcohol syndrome, alcohol-related birth defects, alcohol-related neurodevelopmental disorder, and spontaneous abortion. The objective of this study was to determine whether the selectively bred genetic drinking Myers High Ethanol Preferring (HEP) rat would continue to drink through pregnancy. Rats from the F7 generation were screened by a 10-day 3-30% (v/v) ethanol concentration 'step up' procedure in order to determine the concentration which resulted in maximal drinking with an ethanol solution to total fluid ratio closest to 0.5. After baseline drinking of the preferred concentrations was established, female HEP rats were randomly selected for mating and their ethanol bottles were removed. Upon finding a 'sperm plug', male rats were removed and the ethanol was returned. A second group received injections of progesterone in sesame oil beginning with a 1.0 mg/kg/day dose which was increased to 3.0 mg/kg/day on gravid days (GD) 5-20. Vaginal smears confirmed that progesterone rendered the rats anoestrous. Neither pregnancy nor progesterone changed either the amount or proportion of ethanol consumed compared to the baseline period. The rats drank an average of 8.4 g/kg daily throughout pregnancy. A sharp drop in food intake was noted the day after mating. Beginning on GD 13, it was observed that pregnant rats showed a marked increase in the variance for proportion of ethanol consumed and body weight. Subsequently, only one of the eight impregnated rats successfully delivered a litter. The ethanol solution was removed and these rats mated again: seven of the eight rats delivered litters. These two findings suggest that the pregnant females must have begun to lose their litters on or after GD 13. Further, pregnancy does not affect the consumption of ethanol in the HEP rat. In addition, due to the fact that drinking by HEP rats during pregnancy leads to such a high rate of resorption of the fetus, this hybrid strain may also constitute a useful model for the study of alcohol-induced spontaneous abortion.

Sex hormones in alcohol consumption: a systematic review of evidence

“…Animal studies, however, revealed no significant impact of progestins administration (progesterone or allopregnanolone) on alcohol consumption in female rats (Almeida et al 1998;Wolfe, Means, & McMillen 2000;Sinnott, Phillips, & Finn 2002). In male animals, a dose-dependent increase of alcohol intake was reported with progestins use regardless of the route of administration (e.g.…”

Emergence of sex differences in the development of substance use and abuse during adolescence

“…A provocative animal study showing that cocaine self-administration diminished dramatically in pregnant rodents, only to resume after pregnancy, suggests biological factors contribute to decreased consumption by women during pregnancy (Hecht, Spear, & Spear, 1999). However, mixed data on consumption of alcohol by high-drinking rat and mouse strains during pregnancy has been published with some studies showing no change and some studies showing decreases (Brady, Allan, & Caldwell, 2012; Kleiber, Wright, & Singh, 2011; Wolfe, Means, & McMillen, 2000). As pregnancy/onset of family responsibilities occurs only after puberty, this could contribute to the emergence of sex/gender differences in drug taking that will be explored below.…”