The Effects of Gonadectomy on Age- and Sex-Typical Patterns of Ethanol Consumption in Sprague-Dawley Rats

Abstract

Background Ethanol intake levels characteristic of adult males and females emerge post-pubertally. The present set of experiments examined the consequences of pre-pubertal and adult gonadectomies to explore whether the presence of gonadal hormones at puberty exerts organizational influences and/or plays an activational role in age- and sex-typical patterns of ethanol consumption. Methods Male and female Sprague-Dawley rats were gonadectomized (GX), received sham gonadectomy (SH) or were left non-manipulated (NM) at one of two ages, either pre-pubertally on postnatal day (P) 23 (early) or post-pubertally in adulthood on P70 (late). Early surgery animals were tested for ethanol consumption either during adolescence (P28-39) or in adulthood at the same age that late surgery animals were tested (P75-86). Voluntary ethanol consumption was indexed using a 2 hr limited-access paradigm, with access to two bottles: one containing water, and the other a sweetened ethanol solution. Results Age of GX did not impact patterns of ethanol consumption. Removal of testicular hormones in males, regardless of age of removal, elevated consumption levels in adulthood to female-typical levels. Ovariectomy did not have notable effects on ethanol drinking in females. Ethanol intake and preference of early SH males was significantly greater than that of both late SH and NM males. Removal of the gonads prior to puberty did not influence ethanol drinking or preference during adolescence in either males or females. Conclusions These results suggest that testicular hormones play an activational role in lowering ethanol intake and preference of adult male rats. Pubertal hormones, in contrast, were found to exert little influence on ethanol drinking or preference during adolescence, although the effect of surgical manipulation itself during development was found to exert a long-lasting facilitatory effect on ethanol consumption in adulthood.

The Teenage Brain

“…Work using this approach has found that animals that do not experience normal developmental increases in pubertal hormones exhibit deficits in later expression of a variety of reproductive behaviors and other adult-typical, sexually dimorphic behaviors (see Sisk & Zehr, 2005, for review). In contrast, we have found pubertal hormones to exert surprisingly modest influences on alcohol intake and sensitivity (Vetter-O’Hagen & Spear, 2011, 2012). For instance, gonadectomy in males (but not females) either prepubertally or in adulthood increased alcohol intake in adulthood, an increase largely reversed by testosterone replacement (Vetter-O’Hagen & Spear, 2011; Vetter-O’Hagen, Sanders & Spear, 2012); this pattern of findings is consistent with an activational role of testosterone in adulthood rather than pubertally-related processes.…”

“…In contrast, we have found pubertal hormones to exert surprisingly modest influences on alcohol intake and sensitivity (Vetter-O’Hagen & Spear, 2011, 2012). For instance, gonadectomy in males (but not females) either prepubertally or in adulthood increased alcohol intake in adulthood, an increase largely reversed by testosterone replacement (Vetter-O’Hagen & Spear, 2011; Vetter-O’Hagen, Sanders & Spear, 2012); this pattern of findings is consistent with an activational role of testosterone in adulthood rather than pubertally-related processes. Moreover, neither pre-pubertal or adult gonadectomy altered sensitivity to alcohol’s social inhibitory effects, although the microstructure of social behavior was affected in both males and females (Vetter-O’Hagen & Spear, 2012).…”

The ontogeny of ethanol aversion

“…see Spear, 2000 for a review). Prominent developmental alterations include ontogenetic increases in control of subcortical regions by the prefrontal cortex (Crews et al, 2007), as well as maturational changes in connectivity between subcortical regions critical for processing rewarding (e.g., nucleus accumbens) and aversive (e.g., the amygdala) stimuli during adolescence, with such regions shown, under certain circumstances, to exhibit greater reactivity to rewarding and emotional/affective stimuli than evident in adulthood (see Spear, 2011). It is possible that the maturational changes in reward and aversion neurocircuitry may contribute to increased alcohol intake in adolescence, as the overall hedonic value of a drug is thought to be a function of the balance between its rewarding and aversive effects (Riley, 2011; M.…”

Sex hormones in alcohol consumption: a systematic review of evidence

“…Most of the animal studies seem to provide more consistent support for a positive relationship between estrogen levels and alcohol intake (Forger & Morin 1982;Mello et al 1986;Roberts et al 1998;Reid et al 2002;Ford et al 2002aFord et al , 2004Marinelli et al 2003;Reid et al 2003;Quirarte et al 2007;Rajasingh et al 2007;Sherrill et al 2011;Torres et al 2014), except for a few studies, which found opposite or no effect (Sandberg & Stewart 1982;Cailhol & Mormede 2001;Ford, Eldridge, & Samson 2002b;Vetter-O'Hagen & Spear 2011). Careful consideration of the differences in the study methodology, such as the route of estrogen administration and ovariectomy, as well as the inter-species differences in estrous cycles is needed when comparing results between those studies or studies in human females.…”