The effects of gonadectomy on sex- and age-typical responses to novelty and ethanol-induced social inhibition in adult male and female Sprague-Dawley rats

Abstract

Sex- and age-typical responses to ethanol and novel stimuli tend to emerge postpubertally, suggesting a potential organizational or activational role for pubertal hormones in these behaviors. To test this possibility, male and female rats were gonadectomized (GX) or received sham gonadectomy (SH) either prepubertally on postnatal day (P) 23 (early) or in adulthood on P70 (late). Animals were tested as adults for response to novelty and, on the following day, challenged with either saline or ethanol (1g/kg) prior to social interaction testing with an unfamiliar partner in a familiar setting under low light conditions. Gonadectomy did not influence ethanol-induced social inhibition in either sex, but instead altered the microstructure of social behavior, with GX animals exhibiting proportionally less time in social investigation and proportionally more time in contact behavior than SH animals, regardless of age of gonadectomy. The early sham surgical manipulation process itself influenced social motivation, with early SH surgery eliminating ethanol-induced decreases in social preference in both sexes. Response to novelty was unaffected by gonadectomy, but was suppressed in early compared to late SH manipulated animals. These results suggest that adult-typical responses to ethanol and novelty-directed behaviors are little influenced by gonadal hormones during puberty or in adulthood. However, the experience of surgical manipulation itself during development exerts behavioral and pharmacological consequences that last into 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).…”

“…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). Studies such as these support the suggestion that adolescent-typical alcohol sensitivities are not notably dependent on pubertally-related processes.…”

Female Sprague-Dawley rats display greater appetitive and consummatory responses to alcohol

“…We did not monitor the estrous cycle in alcohol or sucrose responding females. There is evidence in support of [44] and against [45–47] the influence of ovarian hormones on alcohol self-administration. Previous work using Sprague-Dawley females showed no effect of the estrous cycle on alcohol responding under an FR1 schedule [34].…”

The ontogeny of ethanol aversion

“…Thus, in this study, CTA to a range of ethanol doses was assessed across a broad age range-- at ages chosen to represent pre-adolescents/juveniles (P23-2 5 ), early (P28-30), mid (P35-3 7 ), and late (P42-44) adolescents, “emerging adults” (P52-54), and adults (P72-74), based on prior literature showing discrete developmental windows within adolescence (e.g. Vetter-O’Hagen et al, 2012; Spear, 2015). Both males (Experiments 1 and 2a) and females (Experiment 2b) were examined.…”